7/5/2016 Systemic vs ocular cancers Cancer and the Eye: • Ocular cancers What you need to know • 2580 new cases each year (primarily melanomas) • 270 deaths Tammy P. Than OD, MS, FAAO • Systemic cancers University of Alabama Birmingham School of Optometry • 1.65 million new cases each year • 589,000 deaths http://www.cancer.org/cancer/eyecancer/deta iledguide/eye-cancer-key-statistics What we are going to talk about Definitions • Cancer basics •Cancer: • How can systemic cancer affect the eyes? • A collection of diseases in which some • What should I be thinking if I see a patient of the body’s cells begin to divide with cancer? without stopping, grow out of control, • What treatments are available for cancer and can become invasive and how can they affect the eyes? • Malignant •Surgery • Can spread into, or invade, nearby •Radiation tissues •Chemotherapy • Differentiated vs undifferentiated 3 4 “Pre-cancerous” changes Categories of cancer • Carcinoma – • Lymphoma – begins most common; in lymphocytes (B- or T- formed by cell) epithelioid cells • Multiple Myeloma – • Sarcoma – form malignant plasma cells in bone and soft • Melanoma tissue • Neuroendocrine - • Leukemia – begin forms from cells that release in bone marrow; hormones in response to a abnormal WBCs signal from the nervous system 5 6 http://www.cancer.gov/about-cancer/what-is- http://www.cancer.gov/about-cancer/what-is-cancer cancer#differences-cancer-cells-normal-cells 1 7/5/2016 Most common cancers Metastasis • Process by which • Increased risk if cancer spreads from tumor cells have the organ of origin aggressive traits on (primary site) to histopathology distant tissues • Poorly differentiated • Disorganized and • Invade beyond normal tissue boundaries invasive-appearing • Spread to regional tumors lymph nodes is one • Cells generally look of the early signs of the same as cells of met potential and/or the original cancer distant spread 8 http://seer.cancer.gov/statfacts/html/all.html Ocular metastases Choroidal metastases • Rare site due to the absence of a lymphatic • Creamy yellow system within the eye subretinal mass, • Spread is via blood, therefore parts of eye often with with greatest vascular supply most likely to be subretinal fluid affected (73%) • Uvea: choroid, esp perimacular choroid • Plateau or dome configuration • But still may be the most common intraocular malignant neoplasm • Unusually large amount of • Based on autopsy data; often not seen subretinal fluid • Optic nerve, retina, vitreous, conjunctiva, orbit for their size can also be affected, but these are rare 9 10 Choroidal metastases Iris • Solitary (72%) • Solid, usually • Avg was 1.6; range white/yellow 1-13 • 74% solitary • Posterior to the •42% inferior equator (92%) •Can shed tumor • Tends to grow rapidly cells that form a • May double in size pseudohyopyon or in a few weeks clog TM and cause glaucoma 11 12 2 7/5/2016 Ciliary body Management • Yellow dome- “Treatment may help prolong the lives of shaped; usually some people with metastatic cancer. In difficult to general, though, the primary goal of visualize clinically treatments for metastatic cancer is to • Inferior location control the growth of the cancer or to 48% of the time relieve symptoms caused by it. Metastatic tumors can cause severe damage to how • May be associated the body functions, and most people who with extensive RD die of cancer die of metastatic disease” and severe ocular pain 13 14 http://www.cancer.gov/about-cancer/what-is- cancer#related-diseases Treatment/management Radiation •External beam •Plaque “The aim of treatment is to restore radiation radiotherapy visual acuity and therefore improve • Lung and breast are • Can be completed most common in a few days the patients’ quality of life for their primary sites, and remaining life span” are radiosensitive • Specialty centers • Readily available • Must be able to • Time consuming: undergo surgery • 5 days/week Cohen VML (2013) • 30 min • For 2-10 weeks 15 16 Other treatments Cancer of Unknown Primary • Systemic chemotherapy • Clinical syndrome • Primary site becomes • May respond, especially to treatments • No primary site is identified obvious in only 5-10% of for breast cancer after standard clinical and patients during their pathological evaluation lifetime. • PDT (Photodynamic therapy) • Exact incidence is • At autopsy, primary site unknown, as many of the identified in ~ 75% of • Best for solitary metastases patient are “assigned” patients. other diagnoses • Primary sites in the • Intravitreal anti-VEGF • May account for 5% of all pancreas, lung, • Best for small, well-circumbscribed mets invasive cancers colorectum and liver without exudative RDs • Usually present with account for 60% of advanced cancer. cases. Breast, ovary, or • Especially good for colon cancer prostate are rare. 17 18 Greco FA, Hainsworth JD, 2011 3 7/5/2016 Paraneoplastic syndromes Paraneoplastic syndromes • Group of rare disorders • Symptoms may be • Nervous and visual system • Can cause a host of (~10%) that are triggered endocrine, are rare, affecting as few neurologic symptoms: as 0.01% of patients by an abnormal immune neuromuscular, • Difficulty walking, system response to a musculoskeletal, • Occurs when an immune swallowing, or talking cancerous tumor cardiovascular, response is mounted to • Loss of muscle tone or fine cutaneous, hematologic, motor ability • Disorders arise from tumor cancer antigens; these gastrointestinal, or renal cancer-fighting antibodies • Memory loss, dementia, secretion of hormones, seizures • May in part explain & T-cells mistakenly attack peptides, or cytokines OR • In the eye, they disrupt immune cross-reactivity some of the most normal cells in the nervous common symptoms of system - including brain, normal cellular function, between tumor and normal and ultimately cause host tissues cancer, such as fatigue, spinal cord, peripheral anorexia, and weight nerves or muscle – or the visual dysfunction. • Most common in individuals loss. eye with lung, ovarian, lymphatic, or breast cancer 19 20 Rahimey E, Sarraf D (2013) Rahimey E, Sarraf D (2013) Cancer-associated retinopathy Cancer-associated retinopathy • Likely most common of the intraocular PNS • Precedes diagnosis of underlying cancer in • Painless visual loss, developing over weeks to about 50% of patients months • Diagnosis made by labs (anti-retinal antibody • Symptoms: photosensitivity, photopsia, glare, testing) and ERG (severely reduced to poor central and color vision (cones) OR extinguished) nyctalopia, impaired dark adaptation, ring • No effective treatment - long-term scotoma, or other peripheral field loss (rods) immunosuppresion is the main therapy – but • Fundus findings normal, or optic nerve pallor, visual prognosis is poor; vision loss is often attenuated retinal arterioles, and RPE thinning rapid and relentless. and mottling • Treatment of underlying malignancy does not appear to be effective 21 22 Rahimey E, Sarraf D (2013) Rahimey E, Sarraf D (2013) Take home points Basic Principles of Therapy • Systemic cancer is prevalent in the population, and will continue to be increasingly prevalent •Staging guides therapy • Metastases to the eye are most common in the choroid, but can occur anywhere in the eye •TNM • 75% of the time the primary site will be the lung or breast •Multimodality treatment • Patients with cancer and new complaints of blurred vision or eye pain should be evaluated •Cure versus Comfort • Although rare, be aware of the clinical entities of paraneoplastic syndrome and CAR •Risk versus Benefit 23 4 7/5/2016 Surgery Radiation Therapy: The Basics • Localized malignancy • Administration • Surgery alone for • Teletherapy ~25% of patients • Brachytherapy • May be palliative • I-125, Sr-90, Ru-106 • Ocular complications • Targets DNA - impairs division can occur • Dependent upon tissue • free radicals generated excised • Intensity Modulated Radiation Therapy • Spectacle considerations (IMRT) Radiation Therapy: Radiation Therapy: The Basics Treatment Considerations • Rad = unit of absorbed energy in •Fraction Size tissue • < 225 cGy / day • Gray (Gy) = 100 Rad • Fractionation Schedule • the “latest” unit • 5 days / week for 2-7 weeks • beam is on for 1-2 minutes • 1 Gy = 100 cGy • Hyperfractionation • Chest X-Ray is < 1 cGy • Cancer treatment may be 6000 cGy • Fraction size is key! Radiation Therapy: Radiation Therapy: Tumors to Treat Treatment Considerations Tissue Dose, cGy •High radiosensitivity Brain 6000 • High mitotic activity Spinal Cord 4500 • Highly vascularized Heart 4500 Intestine 4500 Liver 3000 Lung 2000 Kidney 2000 Bone Marrow 250 5 7/5/2016 Radiation Therapy: Radiation Therapy: Acute Radiation Sickness Long Term Complications •GI upset • Tend to be progressive •N/v • Diarrhea • Can occur years after •Anemia treatment • Depends on area radiated • Incidence increases with: •Skin rashes • More fractions • Alopecia - localized • Larger fractions •Fatigue • Higher total dose Radiation Complications: Radiation Complications: Anterior Segment Diagnosis and Management • Focal radiation • Eyelids • Head/neck delivery • Conjunctiva • Total body irradiation •Lacrimal • Prior to bone marrow transplantation • 13% (N=397) had posterior segment system complications •Cornea • Hemibody irradiation • Decreases diffuse bone pain •Iris • Treats multiple disease sites •Sclera • May require treatment of other half •Lens Radiation Complications: Eyelid Epiphora • Telangiectasia • Causes secondary to radiation: • Madarosis •KCS • Transient • Permanent (>50 gy) • Pseudo-epiphora