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 Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 2  |  Issue : 1  |  Page : 2

Intravitreal bevacizumab for choroidal metastases secondary to adenocarcinoma of the lung


1 Department of Ophthalmology, Northwestern University Feinberg School of Medicine; Department of Surgery, Division of Ophthalmology and Visual Sciences, The University of Chicago, Chicago, IL, USA
2 Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Date of Submission28-Oct-2014
Date of Acceptance20-Apr-2015
Date of Web Publication11-Jun-2015

Correspondence Address:
Manjot K Gill
Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL
USA
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Source of Support: Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY, Conflict of Interest: None


DOI: 10.4103/2393-8633.158512

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  Abstract 

To present a case of choroidal metastases from lung adenocarcinoma treated with intravitreal bevacizumab prior to external beam radiotherapy and systemic chemotherapy. Retrospective interventional. A 72-year-old male, with no significant past ocular or medical history, presented with decreased visual acuity (VA) and a relative scotoma in his left eye. Clinical examination revealed an elevated subretinal lesion in the superotemporal macula in the left eye with fovea-involving subretinal fluid (SRF). Systemic workup revealed metastatic primary adenocarcinoma of the lung. The patient was treated with two intravitreal bevacizumab injections 5 days apart. However, given persistent SRF, external beam radiation and systemic chemotherapy were initiated, which yielded a resolution of SRF, involution of the lesions, and restoration of VA. Although anti-vascular endothelial growth factor (anti-VEGF) therapy represents a therapeutic option for choroidal metastases, enthusiasm for positive results should be tempered. Anti-VEGF agents may be used as adjuncts with other modalities such as external radiotherapy and systemic chemotherapy in the management of such lesions.

Keywords: Bevacizumab, choroidal metastases, lung adenocarcinoma


How to cite this article:
Gupta N, Shah AM, Jampol LM, Gill MK. Intravitreal bevacizumab for choroidal metastases secondary to adenocarcinoma of the lung. Carcinomics Clin Commun 2015;2:2

How to cite this URL:
Gupta N, Shah AM, Jampol LM, Gill MK. Intravitreal bevacizumab for choroidal metastases secondary to adenocarcinoma of the lung. Carcinomics Clin Commun [serial online] 2015 [cited 2019 Mar 20];2:2. Available from: http://www.carcinomics.org/text.asp?2015/2/1/2/158512


  Introduction Top


Choroidal metastases represent the most common intraocular malignancy in adults and may be seen in up to 12% of metastatic carcinomas, [1] most frequently from lung and breast in men and women, respectively. Treatment options include enucleation, systemic chemotherapy, external beam radiotherapy, plaque brachytherapy, and photocoagulation. Recently, there have been case reports discussing the use of anti-vascular endothelial growth factor (anti-VEGF) agents as well as photodynamic therapy in the treatment of choroidal metastases. [2],[3],[4] We present a case of metastatic lung adenocarcinoma treated with intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA, USA).


  Case Report Top


A 72-year-old previously healthy male presented with subacute decreased vision and a relative inferonasal scotoma in his left eye. He had a 3-pack-year smoking history but quit in 1962. He denied weight loss or cough. Visual acuity (VA) was 20/25 OD and 20/60 OS.

Right eye examination revealed an elevated subretinal lesion along the inferotemporal arcade. Left eye findings included an elevated subretinal lesion inferonasal to the optic nerve and a larger elevated pale subretinal lesion in the superotemporal macula extending to the foveola, with fovea-involving subretinal fluid (SRF), which was confirmed with spectral-domain optical coherence tomography (SD-OCT) [Figure 1]. Fluorescein angiography revealed early blockage with a gradual increase in hyperfluoresence. Ultrasonography of the left eye showed an irregular solid mass with moderate to high internal reflectivity. Systemic workup, including positron emission tomography scan and brain magnetic resonance imaging, revealed primary adenocarcinoma of the lung with metastases to the brain, scapula, ribs, and vertebrae giving him a diagnosis of stage IV nonsmall cell lung cancer (NSCLC).
Figure 1: Color fundus photo shows an approximately 2.5 disc diameter elevated, pale subretinal lesion in the superotemporal macula of the left eye upon presentation (left) with noticeable growth of the lesion only 1-week after initial presentation (right) (a). Spectral-domain optical coherence tomography at presentation shows choroidal elevation in the left macula with overlying subretinal fluid (b)

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One week after presentation, all three initial lesions had increased in size with an additional superotemporal lesion in the left eye [Figure 1]. VA decreased to 20/80 OS. Chemotherapy was scheduled for the following week, pending molecular study results. He had also been evaluated by radiation oncology for possible external beam radiotherapy. However, due to worsening VA and lesion growth, the decision was made to attempt intravitreal bevacizumab injections. Informed consent was obtained from the patient. The left eye was treated with bevacizumab at a standard dose of 1.25 mg/0.05 mL. Five days later, there were pigmentary changes overlying the macular lesion [Figure 2]. However, SD-OCT revealed increased SRF associated with all three lesions in the left eye as well as growth of both extramacular lesions. The right eye lesion had also grown, with the development of new SRF. Given these findings and worsening VA (20/100 OS), both eyes were treated with intravitreal bevacizumab at a higher dose of 2.5 mg/0.10 mL.
Figure 2: Color fundus photo shows pigmentation over the macular lesion 1-week after injection of 1.25 mg/0.05 mL intravitreal bevacizumab in the left eye (top). Spectral-domain optical coherence tomography (SD-OCT) at the same time reveals increased subretinal fluid (SRF) at the fovea (bottom) (a). SD-OCT reveals significant decrease in SRF at the fovea with persistent choroidal elevation following six radiation treatments and prior to initiation of systemic chemotherapy (top), resolution of SRF at the fovea with persistent choroidal elevation after 10 radiation treatments and 1 session of systemic chemotherapy with cisplatin, pemetrexed, and bevacizumab (middle), and ultimate flattening of the choroidal lesion after a total of 2 sessions of systemic chemotherapy (bottom) (b)

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On follow-up, lesion sizes were stable. However, given persistent SRF, and further VA deterioration (20/200 OS), the patient underwent bilateral palliative external beam radiation and subsequently, systemic chemotherapy with cisplatin, pemetrexed, and bevacizumab 3 weeks after the last injection, resulting in SRF resolution, involution of the lesions, and restoration of VA to 20/40 OS [Figure 2]. Unfortunately, the patient died shortly thereafter.


  Discussion Top


Treatment of choroidal metastases presents a significant challenge to retina specialists, especially when lesions involve the macula. Decisions must take into account factors including life expectancy, the degree of visual compromise, state of the fellow eye, and patient wishes. Traditionally, systemic chemotherapy and local radiotherapy have been the treatment modalities of choice. Bottke et al. showed that 53% of patients had VA improvement, and 34% remained stable when treated with external beam radiotherapy. [5] Local tumor control was achieved in the vast majority of cases with few secondary effects. In recent years, anti-VEGF agents including bevacizumab and ranibizumab (Lucentis; Genentech, South San Francisco, CA, USA) have gained acceptance in the treatment of ocular disease including exudative age-related macular degeneration, macular edema from venous occlusion, and diabetic retinopathy, and have displayed impressive effects in a number of randomized controlled clinical trials. Kim et al. recently presented a case of complete regression of choroidal metastasis from NSCLC with combined intravitreal bevacizumab and oral erlotinib. [2] These authors, and others, have proposed that inhibition of tumor-induced angiogenesis should prevent growth and potentially cause lesion regression.

A case study of three patients presenting with choroidal metastases as the initial manifestation of NSCLC describes intravitreal bevacizumab as primary ocular treatment in two out of the three patients which, when combined with systemic chemotherapy and brachytherapy, yielded improvement in both, ocular lesions as well as VA. [6] A report by Chen et al. on treatment modalities for choroidal metastases, in which metastatic lesions which grew despite systemic chemotherapy responded well to intravitreal bevacizumab injections, demonstrated the anti-permeability and anti-angiogenic effects of bevacizumab. [7]

In our patient, the rapid appearance of pigmentary changes overlying the macular lesion in the left eye within days following the first bevacizumab injection suggests that treatment, may have had some effect on the tumor, although minor given worsening VA and increase in SRF. Despite a second injection 5 days later at a higher dose, the choroidal lesions did not show significant improvement. Given the rapid onset and progression of the lesions, it is possible that the lesions would have grown even faster without intravitreal bevacizumab and that bevacizumab did, in fact, exert anti-angiogenic and anti-permeability effects on lesion related angiogenesis as has been proposed. [4],[8] The injections may have afforded the necessary time for the patient to be evaluated for systemic treatment including external beam radiation, to which our patient displayed a much more favorable response. Systemic bevacizumab was approved as a first line treatment for nonsquamous NSCLC in combination with platinum-based chemotherapy based on studies and reports showing an improvement in response rate and progression-free survival. [9],[10] Intravitreal bevacizumab may have had an additive benefit to the robust response to radiation and systemic chemotherapy, which included intravenous bevacizumab, acting synergistically to yield beneficial effects.

Treatment with intravitreal bevacizumab may play a role as an adjunct to more established treatment modalities for choroidal metastases and may be most beneficial when initiated simultaneously with systemic treatment, [7] Although therapeutic options for these lesions are increasing, systemic treatment remains the mainstay of treatment and further studies are indicated to determine the optimal use for more localized therapy such as intravitreal bevacizumab with respect to long-term safety and efficacy.

 
  References Top

1.
Fabrini MG, Genovesi-Ebert F, Perrone F, De Liguoro M, Giovannetti C, Bogazzi F, et al. A multimodal approach to the treatment of bilateral choroidal metastases from thyroid carcinoma. Rare Tumors 2009;1:e4.  Back to cited text no. 1
    
2.
Kim SW, Kim MJ, Huh K, Oh J. Complete regression of choroidal metastasis secondary to non-small-cell lung cancer with intravitreal bevacizumab and oral erlotinib combination therapy. Ophthalmologica 2009;223:411-3.  Back to cited text no. 2
    
3.
Amselem L, Cervera E, Díaz-Llopis M, Montero J, Garcia-Pous M, Udaondo P, et al. Intravitreal bevacizumab (Avastin) for choroidal metastasis secondary to breast carcinoma: Short-term follow-up. Eye (Lond) 2007;21:566-7.  Back to cited text no. 3
    
4.
Harbour JW. Photodynamic therapy for choroidal metastasis from carcinoid tumor. Am J Ophthalmol 2004;137:1143-5.  Back to cited text no. 4
    
5.
Bottke D, Wiegel T, Kreusel KM, Bornfeld N, Schaller G, Hinkelbein W. Radiotherapy of choroidal metastases in patients with disseminated cancer. Onkologie 2000;23:572-5.  Back to cited text no. 5
    
6.
Singh N, Kulkarni P, Aggarwal AN, Rai Mittal B, Gupta N, Behera D, et al. Choroidal metastasis as a presenting manifestation of lung cancer: A report of 3 cases and systematic review of the literature. Medicine (Baltimore) 2012;91:179-94.  Back to cited text no. 6
    
7.
Chen CJ, McCoy AN, Brahmer J, Handa JT. Emerging treatments for choroidal metastases. Surv Ophthalmol 2011;56:511-21.  Back to cited text no. 7
    
8.
George B, Wirostko WJ, Connor TB, Choong NW. Complete and durable response of choroid metastasis from non-small cell lung cancer with systemic bevacizumab and chemotherapy. J Thorac Oncol 2009;4:661-2.  Back to cited text no. 8
    
9.
Reinmuth N, Heigener D, Reck M. Novel angiogenesis inhibitors in nonsmall cell lung cancer. Curr Opin Oncol 2015;27:79-86.  Back to cited text no. 9
    
10.
Cabebe E, Wakelee H. Role of anti-angiogenesis agents in treating NSCLC: Focus on bevacizumab and VEGFR tyrosine kinase inhibitors. Curr Treat Options Oncol 2007;8:15-27.  Back to cited text no. 10
    

 
  Authors Top

Dr. Nitasha Gupta: Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Department of Surgery, Division of Ophthalmology and Visual Sciences, The University of Chicago, Chicago, IL, USA.

Dr. Ankur M. Shah: Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Department of Surgery, Division of Ophthalmology and Visual Sciences, The University of Chicago, Chicago, IL, USA.>br>
Dr. Lee M. Jampol: Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.>br>
Dr. Manjot K. Gill: Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.


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