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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
J Thorac Oncol. Author manuscript; available in PMC 2014 February 1.
Published in final edited form as:
PMCID: PMC3552378
NIHMSID: NIHMS418283

A Case Series of NSCLC Patients with Different Molecular Characteristics and Choroidal Metastases: Improvement in Vision withTreatment Including Pemetrexed and Bevacizumab

Introduction

The choroid comprises part of the uveal tract and is the most vascular layer of the eye, lying between the retina and the sclera. Lung cancer is the most common cause of choroidal metastases in men and vision loss occurs via accumulation of subretinal fluid that can lead to retinal detachment1. Herein, we present 3 cases of patients with choroidal metastases with different molecular characteristics that had improvement in vision with systemic treatment with or without radiotherapy (Table 1).

Table 1
Summary of Choroidal Metastases Cases

Case 1

A 36 year-old, non-smoking man presented with right eye vision loss. Ophthalmologic exam revealed a choroidal lesion. MRI of the brain showed a right choroidal mass (Figure 1). Body CT revealed a left upper lobe lung mass, as well as boneand liver metastases. Lung adenocarcinoma was diagnosed on liver biopsy.

Figure 1
Right Eye Choroidal Metastasis on MRI (Arrow).

The patient receivedstereotactic radiation to the choroidal lesion and was started on cisplatin/pemetrexed/bevacizumab with significant improvement in vision and overall diseaseburden. He was able to work fulltime and remained physically active. Molecular analysis showedan EGFR exon 20 insertion and an E542K PIK3CAmutation. He had systemicprogression 12 months laterand was placed on a clinical trial Unfortunately, he experienced continued weight loss and decline in his functional status, consistent with a lack of response to therapy. After two months, he developed increased confusion and seizures. MRI brain showed hydrocephalus and diffuse leptomeningeal disease. He then began home hospice.

Case 2

A 60 year-old man presented with cough and shortness of breath. CT revealed a left lung mass, pulmonary nodules, mediastinal lymphadenopathy, pleural effusions and bone lesions. MRI showed diffuse brain metastases less than 5 mm in size. Lung adenocarcinoma was diagnosed on pleural fluid cytology. Given symptomatic pulmonary disease, carboplatin and pemetrexed were given without waiting for mutation status or brain irradiation, and bevacizumab was deferred in thesetting of untreated brain metastases. Subsequent molecular testing showed an EGFR L858R activating mutation. After three cycles of chemotherapy, he had a systemic partial response, but soon after, presented to the emergency department with right eye vision loss. Ophthalmologic exam showed right eye choroidal metastases. The patient received whole brain radiotherapy with anterior fields incorporating the choroidal region. His vision returned to normal after radiotherapy. He then received carboplatin/pemetrexed/bevacizumab for four cycles followed by pemetrexed/bevacizumab until slight systemic progression after 10 maintenance cycles. He was then started on erlotinib with continued resolution of visual symptoms and no evidence of recurrent choroid metastases on eye exam at the time of this report, over 15 months into therapy.

Case 3

A 42 year-old non-smoking man presented with left eye vision loss. Eye exam showed a choroidal metastasis (Figure 2)and MRI was negative for intracranial disease. Body CTshowed a left lower lobe lung mass, bony metastases and mediastinal adenopathy.

Figure 2
Choroid metastasis from NSCLC on ophthalmologic exam (Arrow).

The patient was started on cisplatin/pemetrexed/bevacizumab followed by pemetrexed/bevacizumab continuation maintenance with improvement in vision until progression noted 16 months later when he developed recurrence of vision loss, bilateral choroidal metastases, new brain metastases, as well as diffuse brain and spine leptomeningeal disease. Mediastinal node biopsy confirmed lung adenocarcinoma withFISH positive for an ALK translocation. He was treated with stereotactic radiationfor his CNS disease and afterwards received crizotinib. After progression on crizotinib 5 months later, he received irinotecanbriefly and then was transitioned to hospice.

Discussion

NSCLC with heterogeneous molecular characteristics can manifest as choroidal metastases. Both systemic chemotherapy and local radiotherapy can improve vision. Treatment including pemetrexed and bevacizumab for systemic therapy contributed to improved vision in all three patients, one of whom had improved, long-term improvement in vision without radiotherapy. The choroid is highly vascular and VEGF inhibition with both systemic and intravitreal bevacizumab have been noted to improve vision loss from choroidal metastases2,3. Since pemetrexed also has CNS activity, it may also be useful in treating choroid metastases, particularly in ALK+ patients who may derive increased benefit from pemetrexed4,5. Two of three patients recurred with leptomeningeal disease highlighting this as a possible pattern of spread from initial choroid disease to eventual progression within the leptomeninges.

Acknowledgments

The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 5 KL2 RR025743(JWR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH

References

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