scholarly journals Implementation of PD-L1 22C3 IHC pharmDxTM in Cell Block Preparations of Lung Cancer: Concordance with Surgical Resections and Technical Validation of CytoLyt® Prefixation

2020 ◽  
Vol 64 (6) ◽  
pp. 577-587
Author(s):  
Si Kei Lou ◽  
Hyang Mi Ko ◽  
Tomonari Kinoshita ◽  
Scott MacDonald ◽  
Jessica Weiss ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Predictive Value ◽  
Interim Analysis ◽  
Lung Tumor ◽  
Intraclass Correlation ◽  
Cancer Center ◽  
Anatomical Site ◽  
Good Reliability ◽  
Surgical Specimen ◽  
Technical Validation

<b><i>Background:</i></b> Programmed death ligand-1 (PD-L1) assessed by immunohistochemistry (IHC) is used as biomarker for pembrolizumab therapy in advanced stage lung cancer patients. However, data permitting direct performance comparison between cytology and surgical specimen types are limited since both specimens from a single tumor site are infrequently available. In addition, alcohol fixation used with cytology specimens requires technical validation of the PD-L1 IHC assay before clinical use. We here report our experience with implementation of the PD-L1 22C3 IHC pharmDx<sup>TM</sup> assay for cytologic samples at a large tertiary cancer center. <b><i>Study Design:</i></b> Archival formalin-fixed (FF), paraffin-embedded cell blocks (CBs) and subsequent lung tumor resections (LTRs) from the same anatomical site were used for a direct comparison of PD-L1 tumor proportion scores (TPSs). TPS values were independently determined by one surgical lung pathologist and two cytopathologists blinded to the specimen pairs. An interim analysis was performed to facilitate the pooling of expertise among observers. After PD-L1 22C3 IHC pharmDx<sup>TM</sup> implementation for FF cytology specimens, dual-processed samples were used for a prospective technical validation of CytoLyt® prefixation (CF). Digital image analysis was performed for a subset of dual-processed specimens. <b><i>Results:</i></b> Eighty-one CBs and LTRs were included for comparison of the specimen types. PD-L1 assessment in CBs had an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 88.9/72.8, 66.7/73.5, 95.2/72.3, 80.0/65.8, and 90.9/79.1% for the ≥50/≥1% cutoff, respectively. The intraclass correlation coefficient was 0.84 (95% confidence interval [CI]: 0.76, 0.90), and it improved after interim analysis (before: 0.79 and after: 0.92). The overall concordance between CF and FF for the categories defined by the ≥50/≥1% cutoff values was 90.4% (95% CI: 79.0, 96.8). Similar assay performance was confirmed by digital analysis. <b><i>Conclusions:</i></b> PD-L1 22C3 IHC pharmDx<sup>TM</sup> shows good reliability if used with CB preparations. CF does not impact assay results significantly. Clinical validation with outcome data is needed, and digital methods of assessment should be further investigated.

Đánh giá hiệu quả sinh thiết u phổi xuyên thành ngực bằng kim dưới hướng dẫn CT-scan

2021 ◽  
Author(s):  
Hung Dung Doan
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Core Needle Biopsy ◽  
Predictive Value ◽  
Needle Biopsy ◽  
Lung Tumor ◽  
Lung Tumors ◽  
Ct Guided ◽  
Core Needle ◽  
Pulmonary Tumors

TÓM TẮT Mục tiêu: Xác định độ chính xác và tỉ lệ tai biến của phương pháp sinh thiết u phổi xuyên thành ngực bằng kim dưới hướng dẫn CTscan. Phương pháp và đối tượng: Hồi cứu, mô tả các bệnh nhân được sinh thiết u phổi xuyên thành ngực bằng kim dưới hướng dẫn CTscan tại bệnh viện Bình Dân từ 3/2019 đến hết 12/2019. Kết quả: Tổng số mẫu là 57 bệnh nhân, nam gần gấp đôi nữ, tuổi trung bình 60,7. Phần lớn bệnh nhân tình cờ phát hiện u phổi (78,9%). U phổi bên phải nhiều hơn bên trái. Kết quả sinh thiết: Ung thư 57,9%; viêm 35,1% và lao 7%. Các trường hợp kết quả sinh thiết là lao: phù hợp với bệnh cảnh lâm sàng, hình ảnh học và được chẩn đoán xác định bởi bác sĩ chuyên khoa lao - Bệnh viện Phạm Ngọc Thạch. Các trường hợp kết quả sinh thiết là viêm: kết quả phẫu thuật là lao 50%, ung thư 20%, viêm 20%. Các trường hợp kết quả sinh thiết là ung thư: so sánh với kết quả phẫu thuật chúng tôi nhận thấy độ nhạy trong phát hiện ung thư phổi của sinh thiết là 85,7%; độ đặc hiệu 100%; giá trị tiên đoán dương 100% và giá trị tiên đoán âm 80%. Tỉ lệ tai biến 21,1% gồm tràn khí màng phổi 12,3%, ho ra máu 7% và tụ máu nhu mô phổi 1,8%. Tỉ lệ tràn khí màng phổi cần dẫn lưu màng phổi cấp cứu là thấp (3,5%). Kết luận: Phương pháp sinh thiết u phổi xuyên thành ngực bằng kim dưới hướng dẫn CTscan khả thi, hiệu quả cao và tương đối an toàn, vì vậy có vai trò quan trọng trong chẩn đoán u phổi. ABSTRACT EVALUATE THE EFFECTIVENESS OF COMPUTED TOMOGRAPHY - GUIDED TRANSTHORACIC CORE NEEDLE BIOPSY OF PULMONARY TUMORS Objectives: The present study aims to determine the diagnostic accuracy of computed tomography (CT) - guided transthoracic core needle biopsy of pulmonary tumorsand the complications of the procedure. Methods: A retrospective descriptive studywas carried out in a series of patients with pulmonary tumors diagnosed by CT - guided transthoracic core needle biopsy at Binh Dan Hospital between 3/2019 and 12/2019. Results: The total sample was 57 patients with an average age was 60.7, male/female = 1.85. Most of the patients were detected lung tumors incidentally (78.9%), and right-side tumors were more than the left - side tumors. Biopsy results included cancer, inflammation, and tuberculosis, with incidence rates were 57.9%, 35.1%, and 7%, respectively. The cases, which were confirmed tuberculosis on biopsy results, were determined tuberculosis by a specialist who worked in Pham Ngoc Thach Hospital. The patients had inflammatory results and were operated on, which had surgical outcomes were tuberculosis (50%), cancer (20%), and inflammation (20%). The cases, which were confirmed cancer on biopsy results after comparing with surgical outcome, found that the biopsy of detecting lung cancer had 85.7% sensitivity, 100% specificity, 100% positive predictive value, and 80% negative predictive value. The rate of complications was 21.1%, including pneumothorax (12.3%), hemoptysis (7%), and pulmonary parenchymal hematoma (1.8%). The rate of pneumothorax requiring emergency pleural drainage was low (3.5%). Conclusions: CT - guided transthoracic core needle biopsy is feasible, highly effective, and relatively safe; therefore, it plays an important role in diagnosing lung tumors. Keywords: Lung tumor, tuberculosis (TB), lung cancer, core biopsy

scholarly journals Comparison of Radiographic Approaches to Assess Treatment Response in Pituitary Adenomas: Is RECIST or RANO Good Enough?

2019 ◽  
Vol 3 (9) ◽  
pp. 1693-1706 ◽  
Author(s):  
Brandon S Imber ◽  
Andrew L Lin ◽  
Zhigang Zhang ◽  
Krishna Nand Keshavamurthy ◽  
Amy Robin Deipolyi ◽  
...  
Keyword(s):  
Treatment Response ◽  
Pituitary Adenomas ◽  
Intraclass Correlation ◽  
Response Assessment ◽  
Outcome Data ◽  
Cancer Center ◽  
Size Change ◽  
Good Reliability ◽  
Volumetric Assessment ◽  
2D And 3D

Abstract Context Pituitary adenomas (PA) are often irregularly shaped, particularly posttreatment. There are no standardized radiographic criteria for assessing treatment response, substantially complicating interpretation of prospective outcome data. Existing imaging frameworks for intracranial tumors assume perfectly spherical targets and may be suboptimal. Objective To compare a three-dimensional (3D) volumetric approach against accepted surrogate measurements to assess PA posttreatment response (PTR). Design Retrospective review of patients with available pre- and postradiotherapy (RT) imaging. A neuroradiologist determined tumor sizes in one dimensional (1D) per Response Evaluation in Solid Tumors (RECIST) criteria, two dimensional (2D) per Response Assessment in Neuro-Oncology (RANO) criteria, and 3D estimates assuming a perfect sphere or perfect ellipsoid. Each tumor was manually segmented for 3D volumetric measurements. The Hakon Wadell method was used to calculate sphericity. Setting Tertiary cancer center. Patients or Other Participants Patients (n = 34, median age = 50 years; 50% male) with PA and MRI scans before and after sellar RT. Interventions Patients received sellar RT for intact or surgically resected lesions. Main Outcome Measure(s) Radiographic PTR, defined as percent tumor size change. Results Using 3D volumetrics, mean sphericity = 0.63 pre-RT and 0.60 post-RT. With all approaches, most patients had stable disease on post-RT scan. PTR for 1D, 2D, and 3D spherical measurements were moderately well correlated with 3D volumetrics (e.g., for 1D: 0.66, P < 0.0001) and were superior to 3D ellipsoid. Intraclass correlation coefficient demonstrated moderate to good reliability for 1D, 2D, and 3D sphere (P < 0.001); 3D ellipsoid was inferior (P = 0.009). 3D volumetrics identified more potential partially responding and progressive lesions. Conclusions Although PAs are irregularly shaped, 1D and 2D approaches are adequately correlated with volumetric assessment.

Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Lung Tumor ◽  
A549 Cells ◽  
Delivery Systems ◽  
Lung Cancer Cells

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

Recombinant adeno-associated virus 9-mediated expression of Kallistatin suppresses lung tumor growth in mice

2020 ◽  
Vol 20 ◽  
Author(s):  
Weihong Qu ◽  
Jianguo Zhao ◽  
Yaqing Wu ◽  
Ruian Xu ◽  
Shaowu Liu
Keyword(s):  
Lung Cancer ◽  
Gene Therapy ◽  
Tumor Growth ◽  
Lung Tumor ◽  
Control Group ◽  
High Dose ◽  
Blank Control Group ◽  
Adeno Associated Virus ◽  
Tumor Tissues ◽  
Subcutaneous Xenograft

Background:: Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure although gene therapy may be a promising future alter-native. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgen-ic expression. Objective:: The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice. Method:: The subcutaneous xenograft mode were induced by subcutaneous injection of 2×106 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single-stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9）by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 stain-ing to evaluate tumor angiogenesis. Results:: Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased. Conclusion:: The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and impli-cate rAAV9-Kal as a candidate for gene therapy of lung cancer.

scholarly journals FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis

Human Cell ◽  
2021 ◽  
Author(s):  
Yan Lu ◽  
Yushuang Zheng ◽  
Yuhong Wang ◽  
Dongmei Gu ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Lung Tumor ◽  
Early Stage ◽  
High Rate ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Metastasis ◽  
Number Of Patients

AbstractLung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.

scholarly journals Tumor mutational burden assessment in non-small-cell lung cancer samples: results from the TMB2 harmonization project comparing three NGS panels

2021 ◽  
Vol 9 (5) ◽  
pp. e001904
Author(s):  
Javier Ramos-Paradas ◽  
Susana Hernández-Prieto ◽  
David Lora ◽  
Elena Sanchez ◽  
Aranzazu Rosado ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Value ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mutational Burden ◽  
Reproducibility Study ◽  
Tumor Mutational Burden

BackgroundTumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays for TMB determination differ in horizontal coverage, gene content and algorithms, leading to discrepancies in results, impacting patient selection. A harmonization study of TMB assessment with available assays in a cohort of patients with NSCLC is urgently needed.MethodsWe evaluated the TMB assessment obtained with two marketed next generation sequencing panels: TruSight Oncology 500 (TSO500) and Oncomine Tumor Mutation Load (OTML) versus a reference assay (Foundation One, FO) in 96 NSCLC samples. Additionally, we studied the level of agreement among the three methods with respect to PD-L1 expression in tumors, checked the level of different immune infiltrates versus TMB, and performed an inter-laboratory reproducibility study. Finally, adjusted cut-off values were determined.ResultsBoth panels showed strong agreement with FO, with concordance correlation coefficients (CCC) of 0.933 (95% CI 0.908 to 0.959) for TSO500 and 0.881 (95% CI 0.840 to 0.922) for OTML. The corresponding CCCs were 0.951 (TSO500-FO) and 0.919 (OTML-FO) in tumors with <1% of cells expressing PD-L1 (PD-L1<1%; N=55), and 0.861 (TSO500-FO) and 0.722 (OTML-FO) in tumors with PD-L1≥1% (N=41). Inter-laboratory reproducibility analyses showed higher reproducibility with TSO500. No significant differences were found in terms of immune infiltration versus TMB. Adjusted cut-off values corresponding to 10 muts/Mb with FO needed to be lowered to 7.847 muts/Mb (TSO500) and 8.380 muts/Mb (OTML) to ensure a sensitivity >88%. With these cut-offs, the positive predictive value was 78.57% (95% CI 67.82 to 89.32) and the negative predictive value was 87.50% (95% CI 77.25 to 97.75) for TSO500, while for OTML they were 73.33% (95% CI 62.14 to 84.52) and 86.11% (95% CI 74.81 to 97.41), respectively.ConclusionsBoth panels exhibited robust analytical performances for TMB assessment, with stronger concordances in patients with negative PD-L1 expression. TSO500 showed a higher inter-laboratory reproducibility. The cut-offs for each assay were lowered to optimal overlap with FO.

scholarly journals Predictive value of pretreatment PD-L1 expression in EGFR-mutant non-small cell lung cancer: a meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhiyu Peng ◽  
Huahang Lin ◽  
Ke Zhou ◽  
Senyi Deng ◽  
Jiandong Mei
Keyword(s):  
Lung Cancer ◽  
Sensitivity Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Value ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutant ◽  
Egfr Tkis

Abstract Objective To investigate the predictive value of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Methods We conducted a systemic search of PubMed, EMBASE, and the Cochrane Library from 1 January 2000 to 30 August 2020, to identify related studies. We combined the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of PD-L1 expression with progression-free survival (PFS) and overall survival (OS). We assessed the quality of the included studies by the Newcastle–Ottawa Scale (NOS). We performed subgroup analyses based on immunohistochemistry (IHC) scoring system, IHC antibodies, sample size, countries, and survival analysis mode. Sensitivity analysis and evaluation of publication bias were also performed. Results Twelve studies including 991 patients met the criteria. The mean NOS score was 7.42 ± 1.19. Patients with high PD-L1 expression was associated with poorer PFS (HR = 1.90; 95% CI = 1.16–3.10; P = 0.011), while there was no association between PD-L1 expression and OS (HR = 1.19; 95% CI = 0.99–1.43; P = 0.070). Subgroup analysis prompted IHC scoring systems, IHC antibodies, and sample size have important effects on heterogeneity. The pooled results were robust according to the sensitivity analysis. Conclusions The result of this meta-analysis suggested that PD-L1 expression might be a predictive biomarker for EGFR-mutant non-small cell lung cancer treated with EGFR-TKIs.

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