- Department of Neurosurgery, Rush University Medical Center, Chicago, United States.
- Department of Ophthalmology, North Shore University Health System, Evanston, Illinois, United States.
- Department of Neurosurgery, North Shore University Health System, Evanston, Illinois, United States.
Correspondence Address:
Ricky H. Wong
Department of Neurosurgery, North Shore University Health System, Evanston, Illinois, United States.
DOI:10.25259/SNI_629_2020
Copyright: © 2020 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.How to cite this article: Andrew K. Wong1, Troy W. Close2, Ricky H. Wong3. Osimertinib-induced rapid regression of large metastatic tumor to the pituitary in a patient with lung adenocarcinoma. 13-Jan-2021;12:13
How to cite this URL: Andrew K. Wong1, Troy W. Close2, Ricky H. Wong3. Osimertinib-induced rapid regression of large metastatic tumor to the pituitary in a patient with lung adenocarcinoma. 13-Jan-2021;12:13. Available from: https://surgicalneurologyint.com/surgicalint-articles/10526/
Abstract
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.
Keywords: Nonsmall cell lung cancer, Osimertinib, Pituitary metastasis, Visual outcomes
INTRODUCTION
Metastatic pituitary tumors are a rare entity comprising only 1–2% of all metastatic lesions. They often signal late stage disease with a median survival time after diagnosis of 10–13 months.[
CASE DESCRIPTION
A 43-year-old male nonsmoker presented with pleuritic chest pain, fatigue, decreased vision, and urinary frequency. Chest computed tomography revealed a right upper lobe lung mass. Positron emission tomography scan revealed additional hypermetabolic foci within the spine and ribs. Percutaneous needle biopsy of the pulmonary lesion was consistent nonsmall cell lung adenocarcinoma. Molecular testing demonstrated EGFR exon 19 deletion. Magnetic resonance imaging (MRI) of the brain revealed a sellar mass with suprasellar extension and compression of the optic chiasm [
Multidisciplinary discussion between neurosurgery, oncology, and ophthalmology considered the differential diagnosis of pituitary macroadenoma versus metastatic disease to the pituitary. The patient was initiated on osimertinib therapy with the standard dose of 80 mg oral dose daily with a plan for close monitoring of symptomatic worsening and re-imaging at 4–6 weeks to evaluate for response and surgical resection of the lesion if necessary.
Visual field examination 1 week after osimertinib initiation was grossly stable with possible slight worsening. Repeat MRI 4 weeks after osimertinib initiation demonstrated complete resolution of the pituitary lesion. Repeat visual field testing found improvement in the previous deficit [
DISCUSSION
With the emergence of targeted genetic therapies we have seen an improvement in our ability to treat NSCLC. One particular class of immunotherapy that has shown success in improving survival is the EGFR-TKIs. In individuals with NSCLC containing mutations in the gene coding for EGFR, EGFR-TKIs are able to block the cellular signal cascade from initiating by binding to the adenosine triphosphate (ATP) binding site of the receptor. First and second-generation EGFR-TKIs target mutations on exons 19 and 21 (Del19 and L858R), but rapidly induce resistance as a result of further mutation on the ATP binding site. Resistance typically occurs in 8–12 months, 50% of which are due to mutations on exon 20 (T790M).[
CNS involvement in metastatic disease is not uncommon, occurring in 20–40% of patients with systemic malignancies.[
Our report is the first to demonstrate the feasibility of treating NSCLC-PitM presenting with signs and symptoms of optic compression with osimertinib. In this case, by initiating EGFR-TKI therapy, we were able to address his systemic disease and potentially the pituitary lesion. Should the pituitary lesion be an adenoma, early initiation of therapy and reduction of systemic tumor burden potentially minimizes perioperative morbidity for subsequent resection. On the other hand, if it is a NSCLC-PitM, in which it ultimately proved to be, it may be treated concomitantly, obviating the need for surgical intervention. Of note, we did observe possible slight worsening of the patient’s vision after initiation of osimertinib that may be further evidence of pseudoprogression that Okauchi et al. had noted.[
While limited to one case, this report may serve as a framework for treating patients with EGFR-mutated NSCLCPitM who present with optic nerve or chiasm compression and visual symptoms. We believe that it is reasonable to initiate EGFR-TKIs with close monitoring for progression of symptoms and follow-up imaging at 4 weeks. This patient will require continued close monitoring for possible recurrence of his sellar lesion.
CONCLUSION
Patients with EGFR-mutated NSCLC metastasis to the pituitary may be considered for EGFR-TKI therapy prior to surgical intervention even in the setting of visual deficits.
Declaration of patient consent
Patient’s consent not required as patients identity is not disclosed or compromised.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Adashek ML, Miller K, Silpasuvan AA. EGFR T790M-positive lung adenocarcinoma metastases to the pituitary gland causing adrenal insufficiency: A case report. Case Rep Oncol Med. 2018. 2018: 2349021
2. Ayeni D, Politi K, Goldberg SB. Emerging agents and new mutations in EGFR-mutant lung cancer. Clin Cancer Res. 2015. 21: 3818-20
3. Ballard P, Yates JW, Yang Z, Kim DW, Yang JC, Cantarini M. Preclinical comparison of osimertinib with other EGFRTKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016. 22: 5130-40
4. Fan W, Sloane J, Nachtigall LB. Complete resolution of sellar metastasis in a patient With NSCLC treated with osimertinib. J Endocr Soc. 2019. 3: 1887-91
5. Javanbakht A, D’Apuzzo M, Badie B, Salehian B. Pituitary metastasis: A rare condition. Endocr Connect. 2018. 7: 1049-57
6. Megyesi JF, Macdonald DR. P14.111 Successful treatment of extensive metastatic disease with successive use of two different EGF receptor antagonists: Case report and review of the literature. Neuro Oncol. 2019. 21: iii94
7. Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. New Engl J Med. 2017. 376: 629-40
8. Okauchi S, Osawa H, Miyazaki K, Kawaguchi M, Satoh H. Paradoxical response to osimertinib therapy in a patient with T790M-mutated lung adenocarcinoma. Mol Clin Oncol. 2018. 8: 175-7
9. Rahmathulla G, Toms SA, Weil RJ. The molecular biology of brain metastasis. J Oncol. 2012. 2012: 723541
10. Shan C, Hong W, Lai M, Wang H, Cai L. CMET-10, Intracranial solitary pituitary metastasis: The implications from five cases. Neuro Oncol. 2019. 21: vi53
11. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH. Osimertinib in untreated EGFR-mutated advanced nonsmall-cell lung cancer. N Engl J Med. 2018. 378: 113-25