Cancer and the Eye Lecture PDF

Cancer and the Eye Nicholas R. Green, OD, FAAO I. Cancer Basics The Cell Cycle Cancer Definition Uncontrolled division of abnormal cells Invade - Circumvent These abnormal cells circumvent the cell cycle and apoptosis Have both genetic (non-modifiable) and environmental (...

Cancer and the Eye Nicholas R. Green, OD, FAAO I. Cancer Basics The Cell Cycle Cancer Definition Uncontrolled division of abnormal cells Invade - Circumvent These abnormal cells circumvent the cell cycle and apoptosis Have both genetic (non-modifiable) and environmental (modifiable) causes Cancer Epidemiology Second leading cause of death in the United States Deaths have declined significantly in the past 30 years due to scientific progress Progress in improving death rates has stalled compared to other chronic diseases Highest among men and African-Americans Social determinants of health play a significant role in survival rates  TNM Staging Tumor, Node, and Metastasis Staging Most used system to describe the severity of cancers T is the size and/or extent of the tumor Information is gathered from a clinical exam, imaging, and /or T0 = no primary tumor, Tis = carcinoma in situ, T1-4 = increasing tumor size and spread surger y N describes lymph node involvement Scores are used to predict N0 = no regional node involvement, N1-3 = increasing number and/or extent of nodal prognosis and dictate treatment involvement options M describes whether there are any distant metastases The higher the scores, the worse M0 = no metastasis, M1 = distant metastasis the prognosis is Def inition s for different stages var y based on the type of cancer p II. Cancer Treatment Surgery Preferred treatment whenever possible Used for diagnosis, staging, curing, and debulking tumors Tissue can be biopsied for more exact diagnoses and treatment plans Radical surgeries include removal of nearby affected structures and lymph nodes Typically combined with other treatment types to improve effectiveness and survival Radiation Use of ionizing radiation to kill cancer cells Created by the loss of particles within an atom which causes it to become electrically charged Attacks the DNA of cells in the mitotic phase of cell division What do you think this means for non-cancerous cells? Doses measured in Gray ’s (Gy’s) Minimal dose to be effective always recommended Doses may be fractioned (divided) over multiple visits Delivered either externally or internally (brachytherapy) External versus Internal Radiation Systemic Side Effects of Radiation Fatigue Skin changes Myelosuppression Decreased production of RBC’s, WBC’s, and platelets Secondary malignancies Why is that? Other side effects based on which organs were targeted Ocular Effects of Radiation Therapy Par ticularly high risk of side Risk Factors effects with orbital, intraocular, Younger patients paranasal, and some neurological radiation Diabetes treatments Hypertension Dosing: Patients also receiving 25-30 Gy can cause chemotherapy minor ocular tissue damage 50+ Gy can cause severe and /or permanent damage Radiation Effects on the Anterior Segment Mad aros is Tr ich ias is E n tr op ion an d / or E ctr op ion Pu n ctal Sten osis Va riou s corn eal ef f ects in clu d in g ed em a, n eovascu lariz at ion , keratin izat ion , an d u lcers Ir itis Cataract f orm ation (u su a lly d elayed 2- 3 years af ter rad iation ) Radiation Retinopathy P r e di c t a b l e c o m p l ic a t i o n o f ra di a t io n tr ea t m e n t D u e t o d a m a g e to vas c u l ar e n d o th e li a l c el ls f r o m t o fr ee ra di c a l s L ea d s t o is c h e m ia a n d r e l a t e d c o m p li c a t io n s Oc c u r s any t im e b et w e e n 1 m o n t h - 1 5 ye a r s a f t e r t r e a tm en t s ta r t e d Hi g h es t r is k b et w e e n 6 m o n t h s a n d 3 ye ar s R i s k Fa c t o r s Hi g h er d o s e s o f ra di a ti o n Does size and location of tumor affect the risk? Oc u la r b ra c hy th e ra p y C a r d iova s c u la r d i s e a s e s s u c h a s d i ab e t e s a n d hy p er te n s i o n Yo un g e r p a t i en t s at h ig h e r r is k f o r p r ol if e ra ti v e d i s e a s e Signs of Radiation Retinopathy Micr oan eur ysm s Hem es Telan g iecta s ia s Har d exu d at es Macu la r ed em a Cott on -wool sp ots Neovas cu la riz a t ion of r etin a , ir is, an g le, an d / or op tic n er ve h ea d Vitr eous h em e Retin a l det a ch m en t Radiation Retinopathy Management Testing Prevention OCT-A Hyper-fractionation of treatment FA Using minimal total radiation FAF needed to get effective Treatment treatment Anti-VEGF injections Eye protection during Sectoral or Pan-retinal laser radiation treatments photocoagulation Prophylactic triamcinolone injections Chemotherapy Use of pharmaceuticals to arrest the reproduction of cancer cells Different classes of drugs will target different stages of the cell cycle Many different routes of administration Can be used in combination with radiation or surgery May be given before surgery to shrink tumor and improve outcomes Causes multiple side effects include nausea, alopecia, vomiting, myelosuppression, and mucositis Ophthalmic Effect(s) Associated Systemic Chemotherapeutic Agents Cornea and conjunctival toxicity (keratitis, corneal deposits, conjunctivitis) Cetuximab, chlorambucil, cyclophosphamide, carboplatin, carmustine, 5FU, methotrexate, cytarabine, tamoxifen, cytosine arabinoside, busulfan, procarbazine, doxorubicin, deoxycoformycin, paclitaxel, erlotinib, trastuzumab, vemurafenib, imatinib Periorbital, orbital, and eyelid toxicity (periorbital edema, orbital Cisplatin, carboplatin, carmustine, cyclophosphamide, cetuximab, docetaxel, inflammation, blepharitis, ectropion/entropion, nasolacrimal duct obstruction) 5FU, methotrexate, cytosine arabinoside, bortezomib, ipilimumab, erlotinib,imatinib, doxorubicin Uveitis Cytarabine, interferon, cyclophosphamide, chlorambucil, ipilimumab, erlotinib, vemurafenib, dabrafenib, trametinib, alpha-interferon Retinal toxicity (pigmentary retinopathy, hemorrhagic retinopathy, serous Tamoxifen, cisplatin, carboplatin, cytarabine, procarbazine, carmustine, retinopathy, macular edema, cotton wool spots, retinal vascular occlusion) docetaxel, alpha-interferon, methotrexate, cytosine arabinoside, ipilimumab, trametinib, imatinib, cobimetinib, trastuzumab, ponatinib, erdafitinib, etoposide Optic nerve toxicity (edema, inflammation, atrophy) Cisplatin, carboplatin, oxaliplatin, carmustine, procarbazine, cyclophosphamide, methotrexate, docetaxel, paclitaxel, tamoxifen, cytosine arabinoside, vincristine, imatinib, alpha-interferon Other neuro-ophthalmic toxicities (cranial nerve palsy, internuclear Cisplatin, plant alkaloids (eg, vincristine), oxaliplatin, carboplatin, carmustine, ophthalmoplegia, nystagmus, transient cortical blindness, or visual field loss) 5FU, methotrexate, cytosine arabinoside, fludarabine Other visual symptoms (vision loss of unclear cause, scintillating ALK inhibitors (eg, crizotinib), paclitaxel, lomustine scotoma, photopsia) Other Types of Cancer Therapy Ta r g e t e d T h e ra py D r ug s th a t t a r ge t s p e c i f ic g e n e ti c a n d m o le c u l ar m ec h a n i s m s o f t h e c a n c e r I n c l u d es m o n oc lo n a l a n t ib o di e s Ho r m on a l T h e ra py U s ed t o t r ea t h o r m o n e- dr i v en t u m o r s B l oc ks t h e h o r m o n e r ec ep t o r s Ha s m u lt ip l e s id e e f f ec t I m m un o t h e ra p y I n c r e a s e s r ec og n i t i o n of c an c er c el ls by t h e i m m u n e s y s t e m M a ke s t h e c e ll s m o r e s u s c ep t i bl e t o c el lu la r c h ec kp o in t s M ay b e u s ed i n c o nj u n c t i o n w i th ra d ia t io n III. Metastasis Secondary Tumors and the Eye Globe and orbit are uncommon sites for metastasis Indicates very poor prognosis Most common structures affected by metastasis is the uveal tract The choroid, overwhelmingly, is the most frequent site affected Why is that? Where in the choroid are metastases most likely to go? Most patients will already have a cancer diagnosis, but this can be the first indication of malignancy Types of Choroidal Melanomas PRIMARY SECONDARY Typically, pigmented Typically, amelanotic Subretinal fluid may be Significant subretinal present fluid larger than the Growth over months to lesion size years Growth within weeks Seeding uncommon Seeding more common in retina and vitreous Secondary Uveal Melanoma Secondary Choroidal Melanoma FUNDUS PHOTOGRAPHY FLUORESCEIN ANGIOGRAPHY Secondary Choroidal Melanoma A AND B SCAN OCT Metastatic Orbital Tumors Uncommon site of metastasis for primar y systemic cancers Comprise up to 13% of all orbital tumors Most secondary orbital tumors come from either breast, lung, or prostate cancers Mean survival time from diagnosis is less than two years Symptoms include pain, diplopia, and vision loss Onset of symptoms is usually very sudden Signs include a mass upon orbital palpation, anterior segment vessel congestion, RAPD, optic nerve edema, and ophthalmoplegia Diagnosis is confirmed with imaging, usually an MRI Signs of Orbital Metastases Imaging for Orbital Metastases IV. Paraneoplastic Disease Paraneoplastic Disease When a malignancy triggers an autoimmune response in another part of the body Patient does not necessarily have to have an active cancer diagnosis Can be diagnosis by detecting autoantibodies in the blood or cerebrospinal fluid (CSF) Ocular Effects of Paraneoplastic Disease MELANOMA-ASSOCIATED BILATERAL DIFFUSE UVEAL RETINOPATHY (MAR) MELANOCYTIC PROLIFERATION (BDUMP) Ocular Effects of Paraneoplastic Disease PARANEOPLASTIC OPTIC NEUROPATHY (PON) OTHER OCULAR EFFECTS Cranial nerve palsy’s Saccadic eye movement deficits Def icits in pursuits Cancer-associated retinopathy (CAR) Cancer-Associated Retinopathy (CAR) Most common ocular paraneoplastic disease A diagnosis of exclusion Most associated with small cell lung, breast, ovarian, endometrial, and cervical cancers Autoantibodies react with the photoreceptors causing their destruction Typically no signs of disease on DFE Insidious onset of symptoms  CAR Signs and Symptoms Symptoms (usually bilateral) Central vision loss Nyctalopia Dyschromatop sia Photopsia and photophobia Signs Uveitis Macular edema Retinal vasculitis Nyctalopia - Night blindness or difficulty of the eye in visualizing under dim light or at night; Daytime vision is unimpaired. CAR Diagnosis and Management TESTING MANAGEMENT OCT Syst emic st eroid s E lect roret in og ram ( E RG ) Syst emic im m u nom od u la tor y Sh ow a g en eralized t herap y d ysf u nc tion Refer ra l to on colog ist if n o can cer Blood t estin g for au t oan tib od ies d iag n os is exis ts A lph a- en oc lose Poor visu al pr og n os is even wit h Recoverin t reat men t Trans du c in Hig h m or t alit y Carb on ic An hyd rase I I Clinical Pearls C a s e h is t o r y q u e s t i o ns fo r c anc e r p at ie n t s s ho ul d inc l ud e : Fa m i l y h i s t o r y o f c a n c e r Ty p e o f c a n c e r Stage Where the cancer has metastasized (if at all) Any treatments performed Re m i s s i o n s t a t u s L oo k c a r e f ul ly f or s ig n s o f m e ta s t a s is a n d p ara n e o pl a s t ic d is ea s e i n a ll c a n c e r p a t ie n ts a nd c an c er s u r vi vo r s A nyon e w it h t h es e c o nd i t io n s , b u t n o c a n c er d ia g n o s i s s h o u ld b e r ef e r r e d t o o n c o lo g y em er g e n t ly B e c o m p a s s io n a t e , b u t f o r t h r ig h t w h en d is c u s s in g t h e s e d ia g no s es wi t h pa t ie n t s  Any Questions?