RESUMEN

OBJECTIVES: Neuregulin-1 (NRG1) fusions may drive oncogenesis via constitutive activation of ErbB signaling. Hence, NRG1 fusion-driven tumors may be susceptible to ErbB-targeted therapy. Afatinib (irreversible pan-ErbB inhibitor) has demonstrated activity in individual patients with NRG1 fusion-positive solid tumors. This study collected real-world data on demographics, clinical characteristics, and clinical outcomes in this patient population. MATERIALS AND METHODS: In this retrospective, multicenter, non-comparative cohort study, physicians in the US-based Cardinal Health Oncology Provider Extended Network collected data from medical records of patients with NRG1 fusion-positive solid tumors who received afatinib (afatinib cohort) or other systemic therapies (non-afatinib cohort) in any therapy line. Objectives included demographics, clinical characteristics, and outcomes (overall response rate [ORR], progression-free survival [PFS], and overall survival [OS]). RESULTS: Patients (N = 110) with a variety of solid tumor types were included; 72 received afatinib, 38 other therapies. In the afatinib cohort, 70.8 % of patients received afatinib as second-line treatment and Eastern Cooperative Oncology Group performance status (ECOG PS) was 2-4 in 69.4 % at baseline. In the non-afatinib cohort, 94.7 % of patients received systemic therapy as first-line treatment and ECOG PS was 2-4 in 31.6 % at baseline. In the afatinib cohort, ORR was 37.5 % overall (43.8 % when received as first-line therapy); median PFS and OS were 5.5 and 7.2 months, respectively. In the non-afatinib cohort, ORR was 76.3 %; median PFS and OS were 12.9 and 22.6 months, respectively. CONCLUSION: This study provides real-world data on the characteristics of patients with NRG1 fusion-positive solid tumors treated with afatinib or other therapies; durable responses were observed in both groups. However, there were imbalances between the cohorts, and the study was not designed to compare outcomes. Further prospective/retrospective trials are required.

Asunto(s)

Neoplasias Pulmonares , Humanos , Afatinib/uso terapéutico , Afatinib/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Cohortes , Fusión Génica , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Neurregulina-1/genética

RESUMEN

We present the first reported case of stage 4 thymoma with pleural metastases that was found to be driven by the neurotrophic tyrosine receptor kinase (NTRK)-fusion gene. The patient was started on chemotherapy but it was discontinued due to intolerable side effects. Alternative options in such patients with rare diseases are limited; in fact, many concerns exist regarding the safety and efficacy of newly approved agents for the treatment of advanced thymomas, such as pembrolizumab and sunitinib. Due to NTRK-fusion gene positivity, entrectinib, a novel NTRK-fusion inhibitor, was then initiated. This drug has shown an objective response of 57% in treating NTRK fusion-positive solid tumors of 19 different histological subtypes, predominantly sarcomas, non-small cell lung cancer (NSCLC), and mammary analogue secretory carcinoma of the salivary gland. However, it has never been assessed in the treatment of thymomas. After 10 months of follow-up, the patient showed a significant response with mild adverse events, which was managed by temporary discontinuation of the drug. This case highlights the crucial role of whole-genome sequencing and tissue-agnostic antineoplastics in the future of cancer treatment.

RESUMEN

Objective:To investigate the clinical features and prognosis of patients with acute myeloid leukemia (AML) with DEK-CAN-positive.Methods:The clinical data of 6 AML patients with DEK-CAN-positive admitted to the First Affiliated Hospital of Zhengzhou University from August 2014 to January 2018 were retrospectively analyzed. Their clinical features, treatment and outcomes were summarized.Results:All 6 patients were female with a median age of 29 years (4-64 years). Among 6 cases, 5 cases were primary granulocytic leukemia partially differentiated (M 2) and 1 case was acute monocyte leukemia (M 5). There were 5 patients with elevated count of white blood cells in peripheral blood, and 1 patient had bone marrow dysplasia, and 2 patients had basophilia. Immunophenotypic analysis showed that all 6 patients were positive for CD34, CD13, CD38 and CD33. Fusion gene detection showed that DEK-CAN was positive and NPM1 mutations were negative in 6 patients; FLT3-ITD mutation was detected in 3 patients and WT1 mutation was detected in 2 patients. Chromosomal karyotyping showed that 2 cases had no split phase and 4 cases carried t(6;9). Follow-up details were available for 6 patients, only 1 patient achieved complete remission after the first course of induction chemotherapy, and the remaining 5 patients had no complete remission after the first course of chemotherapy, and died of complications in a short time. Conclusion:AML patients with DEK-CAN-positive have a very poor prognosis, low primary induced remission rate and high mortality.

RESUMEN

Ewing sarcoma is the second most prevalent malignant primary bone tumor but constitutes only a small proportion of cardiac metastases. We present a case of asymptomatic Ewing sarcoma metastatic to the right ventricle. A 36-year-old man presented for evaluation and resection of a pedunculated right ventricular cardiac tumor. Three years before, he had been diagnosed with translocation-negative Ewing sarcoma, for which he had undergone chemotherapy and amputation of the left leg below the knee. We resected the right ventricular tumor. Analysis of the resected mass supported the diagnosis of metastatic Ewing sarcoma. Postoperative transthoracic echocardiograms showed normal biventricular size and function. One year later, the patient had no recurrence of the sarcoma. In addition to discussing this case, we review the relevant medical literature.

Asunto(s)

Neoplasias Óseas/patología , Neoplasias Cardíacas/secundario , Ventrículos Cardíacos/patología , Sarcoma de Ewing/secundario , Adulto , Biopsia , Neoplasias Óseas/terapia , Procedimientos Quirúrgicos Cardíacos , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/cirugía , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sarcoma de Ewing/diagnóstico por imagen , Sarcoma de Ewing/cirugía , Resultado del Tratamiento

RESUMEN

ObjectiveTo investigate the fusion sequence complexity of EML4-ALK in non-small cell lung cancer (NSCLC) patients,and the potential mutation in tyrosine kinase ( TK ) domain of ALK gene.MethodsIn routine practice,a novel echinoderm microtubule-associated protein-like4 and anaplastic lymphoma kinase (EML4-ALK) V3c variant was detected by rapid amplification of cDNA ends-polymerase chain reaction ( RACE-PCR )-sequencing technology in a patient with NSCLC.The further consecutive 39 cases( total of 40 cases)were screened by use of reverse transcription (RT)-PCR for EML4-ALK fusion.Positive PCR products were purified and cloned into T vectors,transformed into DH5a germ cells and colony picked up and sequenced for sequence complexity analysis.Tyrosine kinase domain of ALK was amplified by RT-PCR and sequenced.ResultsThree out of 40 cases had EML4-ALK fusion.One case had six novel variants of EML4-ALK co-existing,termed as V3c ( 64.6％ ),V3d ( 25.0％ ),V3e ( 2.1％ ),V3f (4.2％ ),V3g(2.1％ )and V3h(2.1％ ) variants,whereas without common V3a and V3b variants.In other two positive cases,one was V1 variant,another was concurrent V2,V3a and V3b variants.No mutations were detected in the TK domain of EML4-ALK in any case.ConclusionsSeveral EML-ALK variants could co-exist in a given lung cancer tissue,which suggest that the diversity and sequence complexity of EML4-ALK fusion are exist.Attentions should be paid to screen all the variants in clinic to improve the pick-up rate.

RESUMEN

Objective To explore the feasibility of inhibitor of apoptosis protein 2-mucosa associated lymphoid tissue lymphoma translocation gene 1 (API2-MALT1) fusion gene detection in endoscopic biopsy tissue of primary gastric lymphoma (PGL), and to study the expression of this fusion gene in PGL and its clinical values in diagnosis and treatment of PGL.MethodsA total of 32 suspicious PGL patients underwent endoscopic ultrasonography (EUS) examination and mucosal biopsy.The biopsy specimens were conducted histopathology examination, immunohistochemistry detection and real time RT-PCR for API2-MALT1 fusion gene expression.The expression of API2MALT1 fusion gene in clearly diagnosed PGL and its relation with PGL diagnosis, classification and treatment were analyzed and summarized.ResultsA total of 14 cases of 32 suspicious PGL patients were diagnosed as PGL by histopathology and immunohistochemistry examination, which including 11 cases of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and 3 cases of gastric diffuse large B-cell lymphoma (DLBCL).There were 5 API2-MALT1 fusion gene positive cases, which were all MALT lymphoma, about 5 out of total 11 MALT lymphoma patients.API2-MALT1 fusion gene expression was negative in all 3 gastric DLBCL cases.The depth of lesion invasion and lymph nodes metastasis were more severe in API2-MALT1 fusion gene negative group than those of positive group.There were 2 of 5 API2-MALT1 fusion gene positive cases were Hp positive, and 5 of 9 negative cases were Hp positive.The anti-Hp therapy in 5 API2-MALT1 fusion gene positive cases was ineffective,however, chemotherapy was effective.In negative group, 2 of 5 Hp positive cases was complete remission and 4 Hp negative cases were ineffective with anti-Hp therapy.ConcltsionsAPI2-MALT1 fusion gene is common genetic abnormality in gastric MALT lymphoma.The detection of this fusion gene expression in endoscopic biopsy specimen by real time RT-PCR is clinically practical, and the detection of this fusion gene is valuable in the assessment of PGL diagnosis, treatment and prognosis.