scholarly journals Hypersensitivity in ALK-positive lung cancers exposed to ALK inhibitors: a case of successful switch to an alternative ALK inhibitor and systematic review of the literature

2018 ◽  
Vol Volume 9 ◽  
pp. 73-77
Author(s):  
Lei Deng ◽  
Janaki Sharma ◽  
Elizabeth Ravera ◽  
Balazs Halmos ◽  
Haiying Cheng
Keyword(s):  
Systematic Review ◽  
Review Of The Literature ◽  
Lung Cancers ◽  
Alk Inhibitors ◽  
Alk Inhibitor ◽  
Alk Positive

Long-term clinical outcomes of ALK inhibitors in patients with ALK-positive advanced non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20542-e20542
Author(s):  
Haruyasu Murakami ◽  
Akira Ono ◽  
Kazuhisa Nakashima ◽  
Shota Omori ◽  
Kazushige Wakuda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Inhibitors ◽  
Alk Inhibitor ◽  
Alk Positive

e20542 Background: Anaplastic lymphoma kinase (ALK) inhibitors show high clinical efficacy in patients with ALK-positive advanced non-small cell lung cancer (NSCLC). However, the long-term clinical outcomes remain unknown. Methods: We retrospectively reviewed medical records of patients with ALK inhibitor-naïve ALK-positive advanced NSCLC who initiated alectinib or crizotinib therapy at the Shizuoka Cancer Center between June 2010 and December 2011. Results: This retrospective study included 14 patients (male/female, 5/9; PS 0/1, 6/8; adenocarcinoma/adenosquamous carcinoma, 13/1; smoker/never smoker, 8/6; brain metastasis presence/absence, 5/9; number of prior chemotherapy regimens 0/1/≥2, 1/7/6; alectinib/crizotinib, 4/10) with a median age of 55 years (range, 28-71). At the data cut-off (January 16, 2017), three patients were still receiving first ALK inhibitors (alectinib in two patients and crizotinib in one). One patient requested the discontinuation of alectinib therapy after five years. One patient discontinued crizotinib therapy due to unacceptable toxicity. Nine patients discontinued first ALK inhibitors due to disease progression. The overall response rate was 78.6% with complete response in two patients (14.3%), partial response in nine (64.3%), stable disease in one (7.1%), and progressive disease in two (14.3%). The median progression-free survival (PFS) for all 14 patients was 15.3 months, and the five-year PFS rate was 35.7%. The five-year PFS rates in patients treated with alectinib and crizotinib were 75.0% and 20.0%, respectively. The median overall survival (OS) for all 14 patients was 36.8 months, and the five-year OS rate was 42.9%. The five-year OS rates in patients treated with alectinib and crizotinib were 75.0% and 30.0%, respectively. Conclusions: ALK inhibitors showed favorable long-term clinical outcomes in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC, especially in patients treated with alectinib.

scholarly journals TRAF1-ALK Fusion Predicts Poor Prognosis for ALK Positive Anaplastic Large Cell Lymphoma Patients with Chemotherapy and ALK Inhibitor

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5224-5224
Author(s):  
Ling Huang ◽  
Xinmiao Jiang ◽  
Hanguo Guo ◽  
Liu Sichu ◽  
Xiaojuan Wei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Poor Prognosis ◽  
Large Cell ◽  
Fusion Partner ◽  
Alk Inhibitors ◽  
Alk Inhibitor ◽  
Alk Positive ◽  
Exon 20

Background: Relapsed/refractory anaplastic lymphoma kinase (ALK) positive anaplastic large cell lymphomas (ALCLs) respond to ALK inhibitors, but resistance, which bear a poor prognosis. No biomarkers were found to predict long duration of response to ALK inhibitors. The ALK gene was first identified as the fusion partner of the nucleophosmin (NPM1) gene in the recurrent t(2;5)(p23;q35) found in a subset of ALCL. However, several distinct ALK fusions which result in highly different characteristics have also been described in lymphomas. Methods: We retrospectively reviewed seven relapsed/refractory ALK positive ALCLs who received ALK inhibitors (six with Crizotinib and one with Alectinib) at Guangdong Provincial People's Hospital from June 2007 through March 2019. We did next generation sequencing (NGS) with paraffin-embedded tissue for two patients who quickly developed resistance. Results: Of the seven patients, four were male and three were female, with a median age of 18 years (range 15-51) old. The median line of therapies was four (range 3-7) and that of ALK inhibitor usage was three (range 2-5). The overall response rate was 7 of 7 (100%) and the median overall survival of 21.2 months (8.5-86 months). Three patients obtained complete response (CR) on Crizotinib and then received autologous stem cell transplantation, and are still CR. One patient obtained CR, but died of serious infection five months after allogeneic stem cell transplantation. One patient is in CR under continuous crizotinib administration. One patient received Crizotinib obtained CR, but three months later got progression disease, the NGS showed TNF receptor-associated factor 1 gene (TRAF1) exon 6-ALK exon 20 fusion junction. The last patient was CR on alectinib, but quickly developed resistance, with a progression free survival of 1 month, the NGS indicated TRAF1 exon 7-ALK exon 20 fusion. Conclusions: ALK inhibitors improved survival of relapsed/refractory ALK positive ALCLs. TRAF1-ALK fusion may predict poor clinical outcome to chemotherapy and ALK inhibitors. This ALK fusion may reflect a trend to aggressive behaviour in lymphomas. Disclosures Li: Guangdong Province Hospital: Employment.

scholarly journals ACT-01 THE SECOND GENERATION ANAPLASTIC LYMPHOMA KINASE (ALK) INHIBITOR CERITINIB EFFECTIVELY INDUCES CELL DEATH IN HUMAN GLIOBLASTOMA CELLS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii13-ii13
Author(s):  
Daisuke Kawauchi ◽  
Masamichi Takahashi ◽  
Shun Yamamuro ◽  
Tatsuya Kobayashi ◽  
Eita Uchida ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Anaplastic Lymphoma Kinase ◽  
Second Generation ◽  
Human Glioblastoma ◽  
Lung Cancers ◽  
Alk Inhibitors ◽  
Anaplastic Lymphoma ◽  
Alk Inhibitor ◽  
Type Gene

Abstract Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase which expresses only in the developmental stage of the brain during embryogenesis of human. On the other hand, a variety of ALK gene alterations, such as oncogenic fusion, activating point mutation, or wild type gene amplification, have been recently discovered as the powerful oncogene in various tumors, and these ALK mutations have also been known as the potential therapeutic targets against tumors harboring these ALK mutations. For example, ALK inhibitors have been already approved and used for the clinical treatment of non-small cell lung cancers harboring oncogenic ALK fusion. Previously, we reported classical ALK inhibitors triggered cell death in human glioblastoma (GBM) cells, which did not express ALK, via suppression of transcription factor STAT3 activation but not in normal tissue-derived cells. In this study, we investigated the anti-tumor effect of newly-developed ALK inhibitors in GBM cells. As a result, a second generation ALK inhibitor ceritinib induced cell death in various human GBM cell lines with lower concentration compared to other ALK inhibitors. Besides, ceritinib also suppressed STAT family activity in these GBM cell lines. From these results, we consider ceritinib might be a novel therapeutic agent against GBMs, and further investigation about the specific anti-tumor mechanism of ceritinib in GBM cells is currently on-going.

scholarly journals The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ricky M. Trigg ◽  
Liam C. Lee ◽  
Nina Prokoph ◽  
Leila Jahangiri ◽  
C. Patrick Reynolds ◽  
...  
Keyword(s):  
High Risk ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Alk Inhibitors ◽  
Anaplastic Lymphoma ◽  
Alk Inhibitor ◽  
Genome Wide ◽  
High Risk Disease ◽  
Alk Positive ◽  
Inhibitor Resistance

AbstractResistance to anaplastic lymphoma kinase (ALK)-targeted therapy in ALK-positive non-small cell lung cancer has been reported, with the majority of acquired resistance mechanisms relying on bypass signaling. To proactively identify resistance mechanisms in ALK-positive neuroblastoma (NB), we herein employ genome-wide CRISPR activation screens of NB cell lines treated with brigatinib or ceritinib, identifying PIM1 as a putative resistance gene, whose high expression is associated with high-risk disease and poor survival. Knockdown of PIM1 sensitizes cells of differing MYCN status to ALK inhibitors, and in patient-derived xenografts of high-risk NB harboring ALK mutations, the combination of the ALK inhibitor ceritinib and PIM1 inhibitor AZD1208 shows significantly enhanced anti-tumor efficacy relative to single agents. These data confirm that PIM1 overexpression decreases sensitivity to ALK inhibitors in NB, and suggests that combined front-line inhibition of ALK and PIM1 is a viable strategy for the treatment of ALK-positive NB independent of MYCN status.

scholarly journals Efficacy of Incremental Next-Generation ALK Inhibitor Treatment in Oncogene-Addicted, ALK-Positive, TP53-Mutant NSCLC

2020 ◽  
Vol 10 (3) ◽  
pp. 107 ◽  
Author(s):  
László Urbán ◽  
Róbert Dóczi ◽  
Barbara Vodicska ◽  
Dóra Kormos ◽  
László Tóth ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Nsclc Patient ◽  
Resistance Mechanisms ◽  
Tumor Control ◽  
Next Generation ◽  
Alk Inhibitors ◽  
Anaplastic Lymphoma ◽  
Alk Inhibitor ◽  
Alk Positive ◽  
Inhibitor Treatment

Background: The anaplastic lymphoma kinase (ALK) gene fusion rearrangement is a potent oncogene, accounting for 2–7% of lung adenocarcinomas, with higher incidence (17–20%) in non-smokers. ALK-positive tumors are sensitive to ALK tyrosine kinase inhibitors (TKIs), thus ALK-positive non-small-cell lung cancer (NSCLC) is currently spearheading precision medicine in thoracic oncology, with three generations of approved ALK inhibitors in clinical practice. However, these treatments are eventually met with resistance. At the molecular level, ALK-positive NSCLC is of the lowest tumor mutational burden, which possibly accounts for the high initial response to TKIs. Nevertheless, TP53 co-mutations are relatively frequent and are associated with adverse outcome of crizotinib treatment, whereas utility of next-generation ALK inhibitors in TP53-mutant tumors is still unknown. Methods: We report the case of an ALK-positive, TP53-mutant NSCLC patient with about five years survival on ALK TKIs with continued next-generation regimens upon progression. Results: The tumor showed progression on crizotinib, but long tumor control was achieved following the incremental administration of next-generation ALK inhibitors, despite lack of evident resistance mechanisms. Conclusion: TP53 status should be taken into consideration when selecting ALK-inhibitor treatment for personalized therapies. In TP53-mutant tumors, switching TKI generations may overcome treatment exhaustion even in the absence of ALK-dependent resistance mechanisms.

Telepractice for Adult Speech-Language Pathology Services: A Systematic Review

2020 ◽  
Vol 5 (1) ◽  
pp. 326-338 ◽  
Author(s):  
Kristen Weidner ◽  
Joneen Lowman
Keyword(s):  
Systematic Review ◽  
Primary Progressive Aphasia ◽  
Future Research ◽  
Service Delivery Model ◽  
Speech Language Pathology ◽  
Review Of The Literature ◽  
Research Designs ◽  
Assessment And Treatment ◽  
Language Pathology ◽  
Screening Assessment

Purpose We conducted a systematic review of the literature regarding adult telepractice services (screening, assessment, and treatment) from approximately 2014 to 2019. Method Thirty-one relevant studies were identified from a literature search, assessed for quality, and reported. Results Included studies illustrated feasibility, efficacy, diagnostic accuracy, and noninferiority of various speech-language pathology services across adult populations, including chronic aphasia, Parkinson's disease, dysphagia, and primary progressive aphasia. Technical aspects of the equipment and software used to deliver services were discussed. Some general themes were noted as areas for future research. Conclusion Overall, results of the review continue to support the use of telepractice as an appropriate service delivery model in speech-language pathology for adults. Strong research designs, including experimental control, across multiple well-described settings are still needed to definitively determine effectiveness of telepractice services.

Acute limb ischemia in a patient with pre-fibrotic myelofibrosis complicated by heparin-induced thrombocytopenia and thrombosis – case report and systematic review of dabigatran use

VASA ◽  
2020 ◽  
pp. 1-6 ◽  
Author(s):  
Marina Di Pilla ◽  
Stefano Barco ◽  
Clara Sacco ◽  
Giovanni Barosi ◽  
Corrado Lodigiani
Keyword(s):  
Systematic Review ◽  
Case Report ◽  
Lower Limb ◽  
Limb Ischemia ◽  
Acute Limb Ischemia ◽  
Review Of The Literature ◽  
Heparin Induced Thrombocytopenia ◽  
Lower Limb Ischemia ◽  
Vein Thrombosis ◽  
Left Lower Limb

Summary: A 49-year-old man was diagnosed with pre-fibrotic myelofibrosis after acute left lower-limb ischemia requiring amputation and portal vein thrombosis. After surgery he developed heparin-induced thrombocytopenia (HIT) with venous thromboembolism, successfully treated with argatroban followed by dabigatran. Our systematic review of the literature supports the use of dabigatran for suspected HIT.

Psychological and Cognitive Aspects of Borderline Intellectual Functioning

2017 ◽  
Vol 22 (3) ◽  
pp. 159-166 ◽  
Author(s):  
Bastianina Contena ◽  
Stefano Taddei
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Intellectual Functioning ◽  
Clinical Impact ◽  
Review Of The Literature ◽  
Borderline Intellectual Functioning ◽  
General Quality ◽  
Meta Analyses ◽  
Over Time

Abstract. Borderline Intellectual Functioning (BIF) refers to a global IQ ranging from 71 to 84, and it represents a condition of clinical attention for its association with other disorders and its influence on the outcomes of treatments and, in general, quality of life and adaptation. Furthermore, its definition has changed over time causing a relevant clinical impact. For this reason, a systematic review of the literature on this topic can promote an understanding of what has been studied, and can differentiate what is currently attributable to BIF from that which cannot be associated with this kind of intellectual functioning. Using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) criteria, we have conducted a review of the literature about BIF. The results suggest that this condition is still associated with mental retardation, and only a few studies have focused specifically on this condition.

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