scholarly journals Osimertinib-induced rapid regression of large metastatic tumor to the pituitary in a patient with lung adenocarcinoma

2021 ◽  
Vol 12 ◽  
pp. 13
Author(s):  
Andrew K. Wong ◽  
Troy W. Close ◽  
Ricky H. Wong
Keyword(s):  
Visual Field ◽  
Surgical Intervention ◽  
Kinase Inhibitor ◽  
Optic Chiasm ◽  
Molecular Testing ◽  
Third Generation ◽  
Sellar Mass ◽  
Visual Deficits ◽  
Visual Field Deficits ◽  
Egfr Mutated

Background: Metastatic nonsmall cell lung cancer (NSCLC) to the pituitary (NSCLC-PitM) is rare and often presents with visual field deficits. Surgical resection for the decompression of the optic apparatus has been the treatment of choice in such cases. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) approved for the treatment of patients with NSCLC with an epithelial growth factor receptor (EGFR) mutation though its role in the treatment of NSCLC-PitM that remains unclear. We present a case of NSCLC-PitM with optic chiasm compression and visual deficits that were successfully treated with osimertinib alone without surgical intervention. Case Description: A 43-year-old male presented with pleuritic chest pain, fatigue, and visual deficits found to have NSCLC and a sellar mass with suprasellar extension and optic chiasm compression. Visual field testing demonstrated associated visual field deficits. Molecular testing was positive for EGFR exon 19 deletion. The patient was started on osimertinib with complete resolution of pituitary lesion and visual deficits at 4 weeks. Conclusion: Osimertinib is a third-generation EGFR-TKI that has demonstrated promising results among patients with metastatic EGFR-mutated NSCLC. While surgery is the mainstay of treatment in patients with a sellar mass, optic compression, and visual deficits, those with EGFR-mutated NSCLC-PitM may benefit from early initiation of such systemic therapies, rather than surgical intervention, with good ophthalmologic results.

Microvascular decompression of the optic chiasm

2011 ◽  
Vol 114 (3) ◽  
pp. 857-860 ◽  
Author(s):  
Nancy McLaughlin ◽  
Michel W. Bojanowski
Keyword(s):  
Visual Field ◽  
Mr Imaging ◽  
Cerebral Artery ◽  
Microvascular Decompression ◽  
Anterior Cerebral Artery ◽  
Visual Fields ◽  
Optic Chiasm ◽  
Visual Deficits ◽  
Visual Field Deficit ◽  
The Right

Elongation of the anterior cerebral artery (ACA) and subsequent compression of the chiasm rarely have been reported as causes of a visual field deficit. Neither has microvascular decompression of the chiasm been described in this circumstance. The authors report on a case of progressive visual deficits caused by compression of the optic apparatus by a right elongated ACA as documented on MR imaging. Microvascular decompression was proposed as treatment. The right A1 segment was larger than usual and tortuous, transmitting its pulsations into the chiasm. A piece of Teflon was inserted between the A1 segment and the chiasm. Following surgery, the visual field deficit progressively improved. At 4 months after surgery, the patient's visual fields were normal. Therefore, an elongated ACA can compress the chiasm and result in a visual field deficit. In such circumstances when facing a progressive visual field deficit, microvascular decompression may improve vision.

Predictor of Visual Impairment Following Paraclinoid Aneurysm Surgery: Special Consideration of Surgical Microanatomy Related to Paraclinoid Structures

2020 ◽  
Vol 20 (1) ◽  
pp. 45-54
Author(s):  
Nakao Ota ◽  
Ioannis Petrakakis ◽  
Kosumo Noda ◽  
Takanori Miyazaki ◽  
Tomomasa Kondo ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Visual Field ◽  
Visual Impairment ◽  
Multivariate Logistic Regression Analysis ◽  
Visual Deficits ◽  
Microsurgical Clipping ◽  
Paraclinoid Aneurysm ◽  
Paraclinoid Aneurysms ◽  
Visual Field Deficits

Abstract BACKGROUND Microsurgical clipping with extradural anterior clinoidectomy (EDAC) for paraclinoid aneurysm is an established technique with good angiographic outcomes, although postoperative worsening of visual acuity remains a concern. Multiple reports show visual acuity deteriorating after clipping, yet the cause remains unclear. OBJECTIVE To analyze results of asymptomatic paraclinoid aneurysm surgeries treated with EDACs, specifically focusing on the microanatomy of paraclinoid structure dissection. This determined the causes of delayed visual impairment and microsurgical indications. METHODS Results of the treatment with EDAC of 94 patients with cerebral aneurysm and normal preoperative visual acuity but also full visual fields were retrospectively analyzed. RESULTS The mean aneurysm size was 6.2 (±3.3) mm. Clipping was performed in 87 cases and trapping in 7 cases. Complete angiographic occlusion was observed in 91 patients. In 26 cases, a postoperative visual deficit occurred. A total of 20 cases exhibited partial visual field deficits, including 5 who were asymptomatic. Visual deficits were only detectable by postoperative ophthalmologic testing. Six showed light perception impairment or blinding. Of the 15 patients with symptomatic partial visual field deficits, 5 showed improvement at follow-up. Visual deficits persisted in 22 patients at the last follow-up. Multivariate logistic regression analysis revealed that medial projecting aneurysm (adjusted odds ratio [OR]: 10.43) and the opening of the carotidoculomotor membrane (adjusted OR: 5.19) were significantly related to visual impairment. CONCLUSION Excess dissection of carotidoculomotor membranes causes postoperative delayed visual worsening. For treating small, asymptomatic paraclinoid aneurysms, carotidoculomotor membranes should not be opened, and microsurgical clipping should not be performed for preoperative asymptomatic medial projecting aneurysms.

scholarly journals Optic nerve compression in craniopharyngioma by taut anterior cerebral arteries visualized in frontal and transsphenoidal exposures: illustrative cases

2022 ◽  
Vol 3 (3) ◽  
Keyword(s):  
Optic Nerve ◽  
Visual Field ◽  
Pediatric Patients ◽  
Anterior Cerebral Artery ◽  
Cerebral Arteries ◽  
Initial Exposure ◽  
Visual Deficits ◽  
Visual Field Deficits ◽  
Optic Nerve Compression

BACKGROUND During initial exposure and removal of craniopharyngioma in pediatric patients with severe visual field deficits, the authors have encountered severe deformation of the optic apparatus by taut anterior cerebral arteries as seen during both frontal craniotomy and transsphenoidal exposures. OBSERVATIONS The authors report two pediatric patients with craniopharyngioma whose severe preoperative visual deficits were associated not only with large suprasellar masses but also with severe optic nerve and chiasm compression by taut anterior cerebral arteries. In each patient, the optic nerves were partially cleft by these vessels’ indenting them. LESSONS The role of a taut anterior cerebral artery complex in compression of the optic apparatus in patients with suprasellar tumors has been reported previously, but the intraoperative images in these two cases dramatically reveal this phenomenon.

Retinotopic organization of the visual cortex before and after decompression of the optic chiasm in a patient with pituitary macroadenoma

2012 ◽  
Vol 117 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Philippe A. Chouinard ◽  
Christopher L. Striemer ◽  
Won Hyung A. Ryu ◽  
Irene Sperandio ◽  
Melvyn A. Goodale ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Visual Field ◽  
Neural Plasticity ◽  
Optic Chiasm ◽  
Pituitary Macroadenoma ◽  
Longitudinal Changes ◽  
Visual Field Test ◽  
Visual Field Deficits ◽  
Before And After ◽  
Retinotopic Organization

Compression induced by a pituitary tumor on the optic chiasm can generate visual field deficits, yet it is unknown how this compression affects the retinotopic organization of the visual cortex. It is also not known how the effect of the tumor on the retinotopic organization of the visual cortex changes after decompression. The authors used functional MRI (fMRI) to map the retinotopic organization of the visual cortex in a 68-year-old right-handed woman before and 3 months after surgery for a recurrent pituitary macroadenoma. The authors demonstrated that longitudinal changes in visual field perimetry, as assessed by the automated Humphrey visual field test, correlated with longitudinal changes in fMRI activation in a retinotopic manner. In other words, after decompression of the optic chiasm, fMRI charted the recruitment of the visual cortex in a way that matched gains in visual field perimetry. On the basis of this case, the authors propose that fMRI can chart neural plasticity of the visual cortex on an individual basis and that it can also serve as a complementary tool in decision making with respect to management of patients with chiasmal compression.

Ponatinib: A Review of Efficacy and Safety

2018 ◽  
Vol 18 (9) ◽  
pp. 847-856 ◽  
Author(s):  
Fulvio Massaro ◽  
Matteo Molica ◽  
Massimo Breccia
Keyword(s):  
Kinase Inhibitor ◽  
Tolerability Profile ◽  
Third Generation ◽  
Efficacy And Safety ◽  
Future Perspectives ◽  
General Management ◽  
T315i Mutation ◽  
Baseline Characteristics ◽  
Management Recommendations ◽  
Cardiovascular Profile

Ponatinib is a third generation kinase inhibitor designed to overcome the gatekeeper T315I mutation. In different trials this drug showed inhibitory activity against native BCR-ABL1 kinase and several ABL1 mutations. For this reason, ponatinib is currently indicated for the treatment of chronic myeloid leukaemia (CML) in every phase of disease resistant and/or intolerant to dasatinib and nilotinib and for whom imatinib is not indicated anymore or for patients with T315I mutation. The drug is also indicated for Ph+ acute lymphoblastic leukaemia (ALL). Ponatinib was temporarily suspended in 2013 for the occurrence of cardiovascular thrombotic events. Since then, different investigators analyzed baseline characteristics of patient candidates for ponatinib, especially cardiovascular profile, in order to describe general management recommendations in this setting. In this review, clinical trials data about the use of ponatinib in CML and Ph+ ALL patients will be discussed. It will be focused also about the safety and tolerability profile of the drug and future perspectives of employment.

scholarly journals Detection of EGFR Activating and Resistance Mutations by Droplet Digital PCR in Sputum of EGFR-Mutated NSCLC Patients

2021 ◽  
Vol 15 ◽  
pp. 117955492199307
Author(s):  
Klaus Hackner ◽  
Anna Buder ◽  
Maximilian J Hochmair ◽  
Matthaeus Strieder ◽  
Christina Grech ◽  
...  
Keyword(s):  
Stable Disease ◽  
Progressive Disease ◽  
Kinase Inhibitor ◽  
Diagnostic Yield ◽  
Resistance Mutation ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Percent Agreement ◽  
Nsclc Patients ◽  
Egfr Mutated

Background: Proof of the T790M resistance mutation is mandatory if patients with EGFR-mutated non-small cell lung cancer (NSCLC) progress under first- or second-generation tyrosine kinase inhibitor therapy. In addition to rebiopsy, analysis of plasma circulating tumor DNA is used to detect T790M resistance mutation. We studied whether sputum is another feasible specimen for detection of EGFR mutations. Methods: Twenty-eight patients with advanced EGFR-mutated NSCLC were included during stable and/or progressive disease. The initial activating EGFR mutations (exon 19 deletions or L858R mutations) at stable disease and at progressive disease (together with T790M) were assessed in simultaneously collected plasma and sputum samples and detected by droplet digital polymerase chain reaction (ddPCR). Results: Activating EGFR mutations were detected in 47% of the plasma samples and 41% of sputum samples during stable disease, and in 57% of plasma samples and 64% of sputum samples during progressive disease. T790M was detected in 44% of the plasma samples and 66% of the sputum samples at progressive disease. In ddPCR T790M-negative results for both specimens (plasma and sputum), negativity was confirmed by rebiopsy in 5 samples. Concordance rate of plasma and sputum for T790M was 0.86, with a positive percent agreement of 1.0 and a negative percent agreement of 0.80. Conclusions: We demonstrated that EGFR mutation analysis with ddPCR is feasible in sputum samples. Combination of plasma and sputum analyses for detection of T790M in NSCLC patients with progressive disease increases the diagnostic yield compared with molecular plasma analysis alone.

scholarly journals Efficacy of the CDK4/6 Dual Inhibitor Abemaciclib in EGFR-Mutated NSCLC Cell Lines with Different Resistance Mechanisms to Osimertinib

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 6
Author(s):  
Silvia La Monica ◽  
Claudia Fumarola ◽  
Daniele Cretella ◽  
Mara Bonelli ◽  
Roberta Minari ◽  
...  
Keyword(s):  
Cell Lines ◽  
Kinase Inhibitor ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Resistant Cell ◽  
Nsclc Cell ◽  
Dual Inhibitor ◽  
Nsclc Patients ◽  
Egfr Mutated

Abemaciclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6 that inhibits the transition from the G1 to the S phase of the cell cycle by blocking downstream CDK4/6-mediated phosphorylation of Rb. The effects of abemaciclib alone or combined with the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib were examined in a panel of PC9 and HCC827 osimertinib-resistant non-small cell lung cancer (NSCLC) cell lines carrying EGFR-dependent or -independent mechanisms of intrinsic or acquired resistance. Differently from sensitive cells, all the resistant cell lines analyzed maintained p-Rb, which may be considered as a biomarker of osimertinib resistance and a potential target for therapeutic intervention. In these models, abemaciclib inhibited cell growth, spheroid formation, colony formation, and induced senescence, and its efficacy was not enhanced in the presence of osimertinib. Interestingly, in osimertinib sensitive PC9, PC9T790M, and H1975 cells the combination of abemaciclib with osimertinib significantly inhibited the onset of resistance in long-term experiments. Our findings provide a preclinical support for using abemaciclib to treat resistance in EGFR mutated NSCLC patients progressed to osimertinib either as single treatment or combined with osimertinib, and suggest the combination of osimertinib with abemaciclib as a potential approach to prevent or delay osimertinib resistance in first-line treatment.

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