A non-small cell lung carcinoma patient responded to crizotinib therapy after alectinib-induced interstitial lung disease / 浙江大学学报·医学版

A 54-year-old, non-smoking woman was diagnosed as stage ⅣB adenocarcinoma with widespread bone metastasis (cT4N2M1c) in the First Affiliated Hospital, Zhejiang University School of Medicine. Immunohistochemistry result showed the presence of anaplastic lymphoma kinase (ALK) gene rearrangement; next-generation sequencing (NGS) indicated EML4-ALK fusion (E6:A20) with concurrent CCDC148-ALK (C1:A20), PKDCC-ALK (Pintergenic:A20)and VIT-ALK (V15:A20) fusions. After 32 weeks of alectinib treatment, the patient complained cough and exertional chest distress but had no sign of infection. Computed tomography (CT) showed bilateral diffuse ground glass opacities, suggesting a diagnosis of alectinib-related interstitial lung disease (ILD). Following corticosteroid treatment and discontinuation of alectinib, clinical presentations and CT scan gradually improved, but the primary lung lesions enlarged during the regular follow-up. The administration of crizotinib was then initiated and the disease was stable for 25 months without recurrence of primary lung lesions and ILD.

Advances in Diagnosis and Treatment of HER2-positive Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is the most common malignancy in the world and the leading cause of cancer death. Human epidermal growth factor receptor 2 (HER2) positive non-small cell lung cancer (NSCLC) refers to the NSCLC caused by mutation, amplification or overexpression of the HER2 gene, resulting in its dysfunction. HER2 is the most active receptor in the HER family and can combine with other members to form dimers, which can activate multiple signaling pathways and regulate cell proliferation, differentiation, migration and apoptosis. In NSCLC, HER2 positivity is usually considered a poor prognostic marker. At present, the diagnosis and treatment of HER2-positive NSCLC are not mature. Immunohistochemistry (IHC), next generation sequencing (NGS) and other technologies are often used to detect the positive status of HER2 mutation, amplification or overexpression. In previous studies, antitumor drugs did not show ideal therapeutic effects in HER2-positive NSCLC. However, in recent years, related researches have shown that antibody-drug conjugates (ADCs) and new tyrosine kinase inhibitors (TKIs) in targeted therapy show good antitumor activity against HER2 positive NSCLC. This article summarized the progress in diagnosis and treatment of HER2-positive NSCLC, so as to provide reference for subsequent researches.
.

Overview of Multiplex Immunohistochemistry and Immunofluorescence Techniques in the Lung Cancer Immunotherapy / 中国肺癌杂志

Lung cancer is the most common malignancy and is a major public health problem worldwide. Programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors provide a new treatment strategy for non-small cell lung cancer (NSCLC). The existing biomarkers all have advantages and defects in selecting patients who benefit from immunotherapy. The multiplex immunohistochemistry/immunofluorescence (mIHC/IF) provides multiplex staining, allows comprehensive studies of cellular composition, cellular functions and cell-cell interactions. A number of studies have used mIHC/IF to explore specific immune cells in tumor immune microenvironment (TIME) and found that it is helpful for clinical prognosis and efficacy prediction in patients with lung cancer. In the era of immunotherapy for lung cancer, this technique has a bright future in translational research and clinical practice. The research progress of mIHC/IF detection in lung cancer immunotherapy is summarized in this review.
.

Clinical significance of multi-sample next-generation sequencing for detection of gene mutations in non-small cell lung cancer / 肿瘤研究与临床

Objective:To explore the clinical significance of multi-sample next-generation sequencing (NGS) in detecting gene mutations in non-small cell lung cancer (NSCLC), so as to provide a basis for individualized targeted treatment.Methods:The data of 51 patients with NSCLC in the First Affiliated Hospital of Zhejiang University Medical College from June 2016 to February 2019 was retrospectively analyzed. The patients' age, gender, smoking status, pathological type, tumor staging, pleural invasion status and meningeal invasion status were collected, and the tissues, cerebrospinal fluid, pleural effusion and plasma samples were detected by NGS. The correlations between the driver gene mutations [epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)] and the clinicopathological features of patients were analyzed by χ 2 test or Fisher exact probability method. Cohen Kappa coefficient analysis was used to compare the consistency of NGS detection results in different samples. Results:Among the 51 patients, 3 different types of specimens were examined in 7 patients. Of which, the driver gene mutations were all positive in 3 cerebrospinal fluid samples and double gene mutations were found in 2 hydrothorax samples. Driver gene mutations were more common in female [90.48% (19/21) vs. 50.00% (15/30), χ 2 = 9.107, P = 0.003], non-smokers [80.00% (24/30) vs. 47.62 (10/21), χ 2 = 5.829, P = 0.016], adenocarcinoma patients [72.34% (34/47) vs. 0, P = 0.017] and patients with malignant pleural effusion [92.86% (13/14) vs. 56.76% (21/37), χ 2 = 4.443, P = 0.035], and the differences were statistically significant. However, there was no statistically significant difference in mutations of driver gene among patients with different age or tumor stages (both P > 0.05). The consistency rate of genetic test results of the driver gene mutations in 37 plasma samples and matched tissue samples was 70.27% (26/37), κ value was 0.430, which suggested a good consistency between them. Conclusions:In patients with advanced NSCLC, gene detection of cerebrospinal fluid is of high application value for patients with meningeal metastasis; for patients with pleural invasion, gene detection of pleural effusion is an effective means to screen targeted therapy drugs. NGS detection of multiple specimens can better reflect the status of gene mutations and guide the individualized targeted therapy of lung cancer patients.

Prognostic Analysis of EGFR-TKIs Combined with Gamma Knife in EGFR-mutant Lung Adenocarcinoma with Brain Metastasis / 中国肺癌杂志

BACKGROUND@#Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery.@*METHODS@#Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on.@*RESULTS@#A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS.@*CONCLUSIONS@#EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.

Progress on the Study of PD-L1 Detection Methods in Non-small Cell Lung Cancer / 中国肺癌杂志

PD-1/PD-L1 inhibitors play an important role in the first-line and second-line treatment of non-small cell lung cancer (NSCLC), indicating a new treatment strategy of NSCLC. Completed clinical trials have shown that effective detection of PD-L1 expression is the key to the use of immunosuppressive agents. However, the gold standard for PD-L1 detection has still lacked. In recent years, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) have been continuously innovated, which accounts for good prospect in PD-L1 detection. The research progress of PD-L1 detection methods in NSCLC is summarized in this review.
.

Clinicopathological characteristics and imaging features of pulmonary adenocarcinoma with micropapillary pattern / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the clinicopathological characteristics and imaging features of lung adenocarcinoma with a micropapillary pattern (MPP).</p><p><b>METHODS</b>Eighty cases of pulmonary adenocarcinoma with a micropapillary pattern treated in our hospital from July 2011 to December 2012 were selected to retrospectively analyze their clinicopathological characteristics and imaging features.</p><p><b>RESULTS</b>Among the 80 cases of lung adenocarcinoma with MPP, there were 38 cases of stage I (47.5%), 12 cases of stage II (15.0%), 25 cases of stage III (31.3%) and 5 cases of stage IV (6.2%). There were 14 cases of moderately differentiated (17.5%) and moderately/poorly differentiated (82.5%) tumors. Sixty-three cases had pleural involvement, vascular invasion, involving the bronchial wall, invasion of large vessels, nerve invasion, and lymph node metastasis (at least one of them) (78.8%). Immunohistochemical staining revealed that both positive rates of TTF-1 and CK7 were 100%, and that of pulmonary surfactant apolipoprotein-A (SPA) was 84.0%. Imaging examination revealed hilar or mediastinal lymph node enlargement in 15 cases (18.8%). but the pathology confirmed hilar or mediastinal lymph node metastasis in 36 cases (45.0%). Lung CT imaging showed that the majority of the cases were peripheral type, and only a few of central type, and most cases were solid lesions, with lobulation, spiculation, pleural indentation, and vascular convergence sign, while there were few ground-glass opacity sign and vacuole sign.</p><p><b>CONCLUSIONS</b>Lung adenocarcinoma with MPP component often presents with early invasions of pleura, blood vessels, lymphatic vessels, and lymph nodes. Imaging manifestation of this cancer mainly shows as peripheral and solid lesions, often with lobulation, spiculation, pleural indentation, vascular convergence sign, but GGO and vacuole signs are unusual. Overexpression of TTF-1, CK7 and SPA, and elevated CEA level are associated with clinical staging of the disease.</p>