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Objective: To investigate the effect of alectinib in the treatment of brain metastases from anaplastic lymphoma kinase(ALK)positive non-small cell lung cancer (NSCLC). Methods: Thirty-four cases of ALK-positive NSCLC in Tianjin Medical University Cancer Institute and Hospital, between August 2016 to October 2019, were retrospectively analyzed. Thirteen cases received first-line single drug therapy (600 mg PO bid) of Alectinib. 7 cases (53.8%) were male, 6 cases were female (46.2%), the median age was 51 (35-72). The Kaplan-Meier method was used to examine progression-free survival (PFS). Results: The median progression-free survival (mPFS) of the alectinib group was 24.5 months, and the adverse drug reactions were mild. Conclusions: The use of alectinibas first-line treatment after the local treatment of measurable intracranial lesions significantly increased the PFS of patients with brain metastases from ALK-positive NSCLC.
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Objective: To investigate the prognostic value of chest computed tomography (CT) characteristics in crizotinib-treated pa-tients with advanced non-small cell lung cancer (NSCLC). Methods: Forty-seven patients with advanced ALK-rearranged NSCLC who re-ceived crizotinib treatment from January 2014 to March 2017 were enrolled in this retrospective study. Pre-treatment CT characteris-tics were evaluated. Patients were followed up after crizotinib treatment, and the best overall response and progression-free survival (PFS) were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Results: The median PFS of all patients was 10 months. There was no association between CT characteristics and response. In univariate analysis, large tumor size (P=0.009), central type (P=0.002), consolidation of surrounding lung tissue (P=0.002), pleural effusion (P=0.001), and lymphangitic carcino-matosis (P=0.019) suggested a poor prognosis. Multivariate Cox regression analysis showed that location (hazard ratio, 3.219; 95% con-fidence interval: 1.517-6.833; P=0.002) was an independent prognostic predictor. Conclusions: Pre-treatment CT characteristics are useful in predicting the PFS of crizotinib-treated patients with advanced NSCLC harboring ALK rearrangement.
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Rizotinib is a first-generation anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) and plays an important role in the treatment of ALK-positive advanced non-small cell lung cancer (NSCLC). However, as with other TKIs, resistance development can-not be avoided with crizotinib. This led to the development of second generation ALK-TKIs such as alectinib, ceritinib, and brigatinib. This article reviews the research progress on treatment of ALK-positive NSCLC with alectinib, which is one of the hotspots.
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Molecular target therapy is one of the most popular field of non-small cell lung cancer (NSCLC) treatmnet. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearragement are the most important two oncogenic drivers in NSCLC, early studies suggested that EGFR mutations and ALK rearrangements are mutually exclusive, but isolated cases or small sample research with concomitant EGFR and ALK alterations have been constantly reported. The co-occurrence of EGFR mutations and anaplastic lymphoma kinase (ALK) rearrangements constitutes a rare molecular, the frequency of EGFR/ALK co-alterations was about 1%, however, little has been known about clinicopathologic feature and treatment. This review summarized published case report, EGFR and ALK alterations are common in female, Asian origin, never smoker, IV stage, and denocarcinomas. First-line treatment can choose EGFR or ALK tyrosine kinase inhibitors (TKIs). However, studies about the origin and resistance mechanism in EGFR/ALK co-alterations are little, require more experimental and clinical research. .
Subject(s)
Humans , Anaplastic Lymphoma Kinase , Carcinoma, Non-Small-Cell Lung , Diagnosis , Genetics , ErbB Receptors , Genetics , Lung Neoplasms , Diagnosis , Genetics , Mutation , Prognosis , Receptor Protein-Tyrosine Kinases , GeneticsABSTRACT
Objective@#To explore the feasibility of conventional smears and liquid-based cytologic slides of lymphatic metastasis specimens of lung adenocarcinoma acquired by fine needle aspiration cytology (FNAC) to detect the expression of anaplastic lymphoma kinase (ALK/D5F3) by immunocytochemistry (ICC) analysis.@*Methods@#The lymphatic metastasis specimens of 147 lung adenocarcinoma, including 100 liquid-based cytologic slides and 47 conventional smears, were collected in this study. ALK fusion protein was detected by Roche Ventana ICC technology, which was compared with the ALK fusion gene assessed by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR).@*Results@#The positive rate of ALK (D5F3) fusion protein in advanced lung adenocarcinoma acquired by FNAC was 11.6% (17/147), and 10.6% (5/47) and 12.0% (12/100) were reached in conventional smears and liquid-based cytologic slides, respectively.Among 147 cases, 57 cases including 17 positive cases and 40 negative cases were verified by RT-PCR and FISH. The whole coincidence rate reached 96.5% (55/57). The sensitivity and specificity of ALK (D5F3) fusion protein detected in lung adenocarcinoma acquired by FNAC were 94.1% (16/17) and 97.5% (39/40), respectively. The sensitivity and specificity were both 100% (5/5 of sensitivity and 10/10 of specificity) in conventional smears, while 91.7% (11/12) and 96.7% (29/30) in liquid-based cytologic slides.@*Conclusion@#Conventional smears and liquid-based cytologic slides of FNAC samples can be used to perform ICC analysis of ALK (D5F3) expression in advanced lung adenocarcinoma, especially for patients who have no opportunity for surgery or whose resected samples are difficult to form cell block.
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It has been found that multiple solid tumors were positive for anaplastic lymphoma kinase (ALK) currently.ALK might be associated with the genesis,development and prognosis of tumor.It is important to localization accurately diagnose the tumor expressed ALK and the subcellular of positive expression of ALK to underway individual precise therapy on rear rangement type of ALK,diagnosis of carcinoma and prognosis and using of ALK inhibitor.This paper mainly reviews the clinicopathological features of ALK positive tumor and its targeted treatment status.
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Objective To improve the diagnosis and treatment of inflammatory myofibroblastic tumor (IMT) of the urinary tract in pediatric.Methods The retrospective study of 12 IMT was based on information retrieved from Beijing Children's Hospital from January 2006 to July 2015.The literatures of urinary IMT were reviewed.There were 12 cases of urinary IMT, with 8 cases in bladder, 2 in kidney, 1 in ureter and 1 in prostate.Mean age at surgery was 6.4 years old (range 2months-13 years), 6 cases males and 6 females.Tumor resection were performed in 11 patients, biopsy was performed only in 1 patient.Results HE staining revealed diffuse appearing spindle myofibroblastic cells admixed with inflammatory cells.Immunohistochemistry showed positive ration for following markers as ALK (8/12), CK18 (6/12), Desmin (7/12), SMA (8/12), Actin (1/2), Vimentin (9/12).Negative staining were seen for Myoglobin, S-100 and Ki-67 ＜ 20％.Patients were followed up in 10 cases, lost to follow-up in 2;the mean follow-up time was 14.4 months (range 3-31 months).All patients recovered well without relapse or metastasis.Condusions Inflammatory myofibroblastic tumors of the urinary tract in pediatric were rare, without specific characteristic in clinical features and imaging.The main treatment of IMT is complete surgical excision.
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Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare and distinct variant of DLBCL. It is classified as a unique subtype of DLBCL in the 2008 WHO classification of lymphomas. No standard and effective therapeutic regi-men is available for ALK+DLBCL because it shows a more aggressive clinical course and frequent relapse. Therefore, a standardized and individualized treatment is needed to benefit more patients diagnosed with ALK+DLBCL through a multiple disciplinary team. This arti-cle presents a case of an ALK+DLBCL patient who relapsed after transplantation and was successfully treated with the ALK kinase inhibi-tor Crizotinib.
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Primary cutaneous CD30(Ki-1) positive anaplastic large cell lymphoma(ALCL) is a rare subset of cutaneous lymphoma, with a much better prognosis. ALCL is a heterogeneous process that may have a T-cell, B-cell, or indeterminant(null) phenotype and which may or may not express the anaplastic lymphoma kinase(ALK) oncoprotein. We report a case of ALCL in a 72 year old man. About 4 months ago, multiple erythematous firm ulcerative mass and satellite nodules developed on the right lower leg. The skin lesions rapidly increased in number and size. Some lesions became painful and centrally ulcered. The histologic findings showed a diffuse infiltrate of large lymphocytes with large nuclei, prominent and multiple nucleoli, and ample cytoplasm. Immunohistochemical stainings for CD30, CD5 were positive but stainings for LCA, CD3, CD45RO, CD20, cytokeratin, EMA, and ALK were negative. Therefore, we diagnosed our case as CD 30+/ALK- ALCL.