First clinical implementation of Yttrium-90 Disc Brachytherapy after FDA clearance.

PURPOSE: Herein, we study if high-dose-rate (HDR) yttrium-90 (90Y) brachytherapy could be utilized by medical physicists, radiation oncologists, and ophthalmic surgeons. METHODS AND MATERIALS: Yttrium-90 (90Y) beta-emitting brachytherapy sources received United States Food and Drug Administration clearance for episcleral treatment of ocular tumors and benign growths. Dose calibration traceable to the National Institute of Standards and Technology as well as treatment planning and target delineation methods were established. Single-use systems included a 90Y-disc affixed within specialized, multifunction, handheld applicator. Low-dose-rate to high-dose-rate prescription conversions and depth-dose determinations were performed. Radiation safety was evaluated based on live exposure rates during assembly and surgeries. Clinical data for radiation safety, treatment tolerability, and local control was collected. RESULTS: Practice parameters for the medical physicist, radiation oncologist, and ophthalmic surgeon were defined. Device sterilizations, calibrations, assemblies, surgical methods, and disposals were reproducible and effective. Treated tumors included iris melanoma, iridociliary melanoma, choroidal melanoma, and a locally invasive squamous carcinoma. Mean calculated 90Y disc activity was 14.33 mCi (range 8.8-16.6), prescription dose 27.8 Gy (range 22-30), delivered to depth of 2.3 mm (range 1.6-2.6), at treatment durations of 420 s (7.0 min, range 219 s-773 s). Both insertion and removal were performed during one surgical session. After surgery, each disc-applicator- system was contained for decay in storage. Treatments were well-tolerated. CONCLUSIONS: HDR 90Y episcleral brachytherapy devices were created, implementation methods developed, and treatments performed on 6 patients. Treatments were single-surgery, rapid, and well-tolerated with short-term follow up.

Early anti-VEGF treatment for radiation maculopathy and optic neuropathy: lessons learned.

Radiation therapy has saved both sight and life for eye cancer patients. The most common methods include ophthalmic plaque brachytherapy and external beam techniques. However, subsequent dose-dependent radiation vasculopathy invariably occurs within and around the targeted zone. In 2006, Finger discovered that periodic intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab could reverse and suppress intraocular radiation vasculopathy. At first, it was administered at the onset of radiation-related vision loss. Though bevacizumab induced regression of macular oedema, retinal haemorrhages and cotton-wool infarcts, most patients were left with residual retinal damage, manifest as metamorphopsia and loss of vision. These results led to earlier and earlier anti-VEGF interventions: first after signs of progressive radiation retinopathy, and then for signs of radiation maculopathy, and finally for high-risk eyes with no clinical signs of retinopathy. Earlier initiation of intravitreal anti-VEGF therapy typically resulted in greater restoration and preservation of macular anatomy, reductions of retinal haemorrhages, resolution of cotton-wool spots and vision preservation. Recent research on optical coherence tomography angiography (OCT-A) has revealed that radiation vasculopathy occurs prior to clinical ophthalmic signs or symptoms. Therefore, it seemed reasonable to consider treating high-risk patients (considered certain to eventually develop radiation maculopathy) to prevent or delay vision loss. Herein, we describe the evolution of treatment for radiation maculopathy as well as recent research supporting anti-VEGF treatment of high-risk patients immediately following radiation to maximize vision outcomes.

Patients presenting with metastases: stage IV uveal melanoma, an international study.

OBJECTIVE: To analyse ocular and systemic findings of patients presenting with systemic metastasis. METHODS AND ANALYSIS: It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. RESULTS: Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. CONCLUSIONS: Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

Palladium-103 plaque therapy for multifocal iris melanoma: Radiation of the entire anterior segment of the eye.

PURPOSE: To investigate the safety and tolerability of total anterior segment palladium-103 (103Pd) eye plaque brachytherapy for multifocal iris melanoma. METHODS: Interventional case series of 11 patients with multifocal iris melanomas. Anterior segment ultrasound revealed tumor size, location, and intraocular margins. Epicorneal amniotic membrane grafts protected the cornea and decreased pain during total anterior segment 103-Pd ophthalmic plaque brachytherapy. RESULTS: Eleven diffuse iris melanomas were American Joint Committee on Cancer 8th edition-classified as T1 (n = 5, 45.5%) and T2 (n = 6, 54.5%). Plaque radiation was completed to a minimum mean tumor dose of 85 Gy (mean dose rate, 58.1 cGy/h). Ultrasonographic tumor thickness regression was 41% (follow up mean 58.7, median 50, range: 8-139 months). Despite 100% local control and 100% eye retention, one patient (9.1%) developed metastatic disease. Four eyes required cataract surgery. There was no corneal stem-cell deficiency, corneal opacity, radiation maculopathy, or optic neuropathy. While visual acuity prior to treatment was 20/40 or better in 10 (91%), 9 were 20/40 or better (81.9%) at last follow-up. Four (36%) had glaucoma prior to treatment and three eyes developed glaucoma after treatment for a total of 63%. CONCLUSION: Total anterior segment (103Pd) plaque brachytherapy resulted in local control, good visual acuity, eye and life preservation in the treatment of multifocal iris melanoma.

Hypochlorous acid antiseptic washout improves patient comfort after intravitreal injection: A patient reported outcomes study.

PURPOSE: Current ocular antiseptic practice for intravitreal injection (IVI) employs 5% povidone-iodine (Betadine®) drops which frequently cause ocular discomfort and prolonged irritation. In an effort to improve comfort while maintaining efficacy, we studied a hypochlorous acid (HOCL 0.01%) spray washout prior to injection. METHODS: Patients had received a minimum of 3 IVIs prepared with Betadine®antisepsis prior to entry in this study. Their subsequent IVIs were prepared with Betadine®followed by HOCL 0.01% washout. Facets of comfort were measured by a Likert-scaled questionnaire to compare their experiences after IVI. RESULTS: Thirty-seven participants were enrolled. Addition of HOCL 0.01% spray after Betadine®reduced the duration of discomfort (P = 0.001) and need for artificial tears postinjection (P = 0.003). It improved their reported quality of life (P = 0.04) and sleep (P = 0.01). There were neither HOCL-related side effects nor endophthalmitis during this study. CONCLUSION: Topical HOCL 0.01% spray after topical Betadine®antisepsis significantly improved patient comfort following IVIs.

Global Tracheostomy Collaborative: data-driven improvements in patient safety through multidisciplinary teamwork, standardisation, education, and patient partnership.

There is growing recognition of the need for a coordinated, systematic approach to caring for patients with a tracheostomy. Tracheostomy-related adverse events remain a pervasive global problem, accounting for half of all airway-related deaths and hypoxic brain damage in critical care units. The Global Tracheostomy Collaborative (GTC) was formed in 2012 to improve patient safety and quality of care, emphasising knowledge, skills, teamwork, and patient-centred approaches. Inspired by quality improvement leads in Australia, the UK, and the USA, the GTC implements and disseminates best practices across hospitals and healthcare trusts. Its database collects patient-level information on quality, safety, and organisational efficiencies. The GTC provides an organising structure for quality improvement efforts, promoting safety of paediatric and adult patients. Successful implementation requires instituting key drivers for change that include effective training for health professionals; multidisciplinary team collaboration; engagement and involvement of patients, their families, and carers; and data collection that allows tracking of outcomes. We report the history of the collaborative, its database infrastructure and analytics, and patient outcomes from more than 6500 patients globally. We characterise this patient population for the first time at such scale, reporting predictors of adverse events, mortality, and length of stay indexed to patient characteristics, co-morbidities, risk factors, and context. In one example, the database allowed identification of a previously unrecognised association between bleeding and mortality, reflecting ability to uncover latent risks and promote safety. The GTC provides the foundation for future risk-adjusted benchmarking and a learning community that drives ongoing quality improvement efforts worldwide.

Predicting the content of anthraquinone bioactive in Rhei rhizome (Rheum officinale Baill.) with the concentration addition model.

Rhei rhizome (Rheum officinale Baill.) (RR) contains a large number of anthraquinone bioactive, yet little is known of the combined effect of these anthraquinones in a mixture. The goals of this study were: to determine the inhibitory potencies of individual anthraquinones and whole RR extract against human liver microsomal CYP1A2/3A4 activity, to predict the content of anthraquinones in RR using the concentration addition (CA) model, and to compare predicted and empirical contents in the same RR sample. Anthraquinone concentrations in the RR extract were determined using HPLC. The inhibitory potencies of individual anthraquinones were determined in incubations containing human liver microsomes. The study results were used to predict an effect-based dose measure of the anthraquinones in RR using the CA model. An empirical dose measure also was determined in the whole RR extract using the CYP1A2/3A4-based bioassay. For the CYP1A2-based studies, the predicted and empirical dose measures of anthraquinones were identical; they were 12.0 ±â€¯1.80 and 12.20 ±â€¯0.81 mg aloe-emodin equivalents/g RR, respectively. For the CYP3A4-based studies, the predicted and empirical dose measures were different; they were 2.80 ±â€¯0.10 and 19.04 ±â€¯0.41 mg aloe-emodin equivalents/g RR, respectively. Only the CYP1A2-based CA model which assumed additive effects of RR anthraquinones predicted an effect-based dose measure that was verifiable by empirical data. The CA model provides an alternative approach to the CYP1A2/3A4-based bioassay or empirical method to screen for the anthraquinones in RR. The CA model as described in this study is applicable to other botanical drugs, plant-based foods and dietary supplements.

Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome.

Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation-specific copy number alterations. Deletions on chr 10q11.21-26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ≤ 0.04), lymphatic invasion (Fisher's exact, p ≤ 0.02), increasing tumor thickness (Mann-Whitney, p ≤ 0.02), and BRAF mutation (Fisher's exact, p ≤ 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.

Expectations for Treatment in Pediatric Weight Management and Relationship to Attrition.

BACKGROUND: Attrition in pediatric weight management negatively impacts treatment outcomes. A potentially modifiable contributor to attrition is unmet family expectations. This study aimed to evaluate the association between adolescent and parent/guardian treatment expectations and attrition. PATIENTS AND METHODS: A prospective, nonrandomized, uncontrolled, single-arm pilot trial was conducted among 12 pediatric weight management programs in the Children's Hospital Association's FOCUS on a Fitter Future collaborative. Parents/guardians and adolescents completed an expectations/goals survey at their initial visit, with categories including healthier food/drinks, physical activity/exercise, family support/behavior, and weight management goals. Attrition was assessed at 3 months. RESULTS: From January to August 2013, 405 parents/guardians were recruited and reported about their children (203 adolescents, 202 children <12 years). Of the 203 adolescents, 160 also self-reported. Attrition rate was 42.2% at 3 months. For adolescents, greater interest in family support/behavior skills was associated with decreased odds of attrition at 3 months [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.57-0.98, p = 0.04]. The more discordant the parent/adolescent dyad responses in this category, the higher the odds of attrition at 3 months (OR 1.36, 95% CI 1.04-1.78, p = 0.02). Weight loss was an important weight management goal for both adolescents and parents. For adolescents with this goal, the median weight-loss goal was 50 pounds. Attrition was associated with adolescent weight-loss goals above the desired median (50% above the median vs. 28% below the median, p = 0.02). CONCLUSIONS: Assessing initial expectations may help tailor treatment to meet families' needs, especially through focus on family-based change and realistic goal setting. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT01753063.

Omalizumab facilitates rapid oral desensitization for peanut allergy.

BACKGROUND: Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. OBJECTIVE: We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. METHODS: Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. RESULTS: The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. CONCLUSION: Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.

Intravitreal anti-VEGF therapy for macular radiation retinopathy: a 10-year study.

PURPOSE: To report long-term experience with intravitreal anti-vascular endothelial growth factor treatment for radiation maculopathy. METHODS: From 2005-2015, 120 consecutive patients underwent intravitreal anti-VEGF therapy for radiation maculopathy. Inclusion criteria included a diagnosis of uveal melanoma treated with plaque radiotherapy and subsequent macular radiation vasculopathy (exudate, retinal hemorrhage, intraretinal microangiopathy, neovascularization, edema). Anti-VEGF therapy involved continuous injections in 4- to 12-week intervals with doses of 1.25 mg/0.05 mL, 2.0 mg/0.08 mL, 2.5 mg/0.1 mL, or 3.0 mg/0.12 mL of bevacizumab as well as 0.5 mg/0.05 mL or 2.0 mg/0.05 mL of ranibizumab. Goals were maintenance of visual acuity and normative macular anatomy. Safety and tolerability (retinal detachment, hemorrhage, infection), visual acuity, central foveal thickness on optical coherence tomography imaging, and clinical features of radiation maculopathy were analyzed. RESULTS: Progressive reductions in macular edema, hemorrhages, exudates, cotton-wool spots, and microangiopathy were noted. At last follow-up, 80% remained within 2 lines of their initial visual acuity or better, with a mean treatment interval of 38 months (range 6-108 months). Kaplan-Meier analysis of the probability of remaining within 2 lines of initial visual acuity was 69% at 5 years and 38% at 8 years of anti-VEGF therapy. Discontinuation of therapy was rare. Relatively few acute or long-term side effects were noted, allowing for good long-term patient accrual. CONCLUSIONS: Continuous intravitreal anti-VEGF therapy in patients with radiation maculopathy was well-tolerated and preserved vision. In most cases, reductions or resolution of retinal hemorrhages, cotton-wool spots, and retinal edema were noted for up to 10 years.

High-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy.

PURPOSE: To evaluate the safety and tolerability and treatment efficacy of high-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy. METHODS: A phase I to II open-label, nonrandomized prospective clinical trial was performed on 10 eyes of 10 patients with recalcitrant radiation retinopathy who were failing standard dose anti-vascular endothelial growth factor (VEGF) therapy. External beam or plaque brachytherapy-associated retinopathy was characterized by persistent macular edema or leakage on optical coherence tomography or fluorescein angiography. Intravitreal 2.0 mg ranibizumab was given monthly up to 12 months and monitored for tolerability and change in best-corrected visual acuity (BCVA), central foveal thickness, and clinical signs of radiation retinopathy. RESULTS: Seven patients completed the 1-year study and received all 12 injections; 3 withdrew from the study due to worsening retinopathy (1 after external beam, 2 following plaque). Treatment was well-tolerated with no severe adverse reactions. A total of 70% had stable (n = 3) or improved (n = 4) BCVA. Mean change in BCVA was +3.3 letters at 6 months and +0.7 letters at 1 year. Mean improvement in central foveal thickness (CFT) was -19.3% (range -57 to +15%) at 1 year. Initial mean CFT was 428 µm (range 192-776); final mean CFT was 333 µm (range 190-532). A total of 80% demonstrated a statistically significant (p<0.05) reduction in CFT. CONCLUSIONS: Regardless of radiation source, intravitreal injections of 2.0 ranibizumab induced significant reductions in macular edema and maintained or improved BCVA in most patients who were failing standard dose anti-VEGF therapy.

Seven new loci associated with age-related macular degeneration.

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

Infected epithelial inclusion cyst simulating conjunctival melanoma.

There are several pigmented nonneoplastic lesions that can clinically simulate melanocytic tumors. The authors report an unusual conjunctival epithelial inclusion cyst that contained luminal bacterial colonies, hemorrhage, and epithelial debris. Clinical appearance convincingly simulated a melanoma. The clinical and histopathologic features of this lesion are discussed.

Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.

PURPOSE: To investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes. DESIGN: Sibling correlation study and genome-wide association study (GWAS). PARTICIPANTS: For the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls. METHODS: Participants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts. MAIN OUTCOME MEASURES: Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes. RESULTS: The difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree (P = 4.2 × 10(-5)), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3 × 10(-9)), which was confirmed in the replication samples (OR, 1.38; P = 7.4 × 10(-14) for combined discovery and replication analysis). CONCLUSIONS: Whether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies.

Expression of neurotrophin receptors by retinoinvasive uveal melanoma.

Retinoinvasive uveal melanoma demonstrates prominent diffuse retinal and optic nerve invasion, with little or no involvement of the adjacent choroid. Prior studies have advanced hypotheses on the potential role of molecular and cellular interactions in the pathogenesis of retinoinvasiveness and neuroinvasiveness, but the precise molecular events are not known. Here, we investigate the role of neutrotrophic factors in the pathogenesis of retinoinvasive uveal melanoma. The records of three ophthalmic pathology departments (The New York Eye and Ear Infirmary, Wills Eye Institute, and University of California San Francisco) were searched to identify all cases of retinoinvasive uveal melanoma, yielding four eyes (all previously irradiated). Eight eyes with nonretinoinvasive melanomas (four irradiated and four nonirradiated) were randomly selected as controls. All enucleated eyes were examined histopathologically and immunohistochemically for the expression of neurotrophic factor receptors [Pan-Trk, p75 neurotrophin receptor (p75(NTR) and ciliary neurotrophic factor receptor-α]. Histopathologic features were similar in both retinoinvasive and control melanomas with regard to choroidal tumor location and size, neovascular glaucoma, and cell type. The eyes with retinoinvasive melanoma showed diffuse retinal invasion beyond the choroidal tumor (n=4) and prelaminar (n=1) and retrolaminar (n=2) optic nerve invasion. The control melanomas showed focal retinal invasion over the tumor apices (n=6) and prelaminar optic nerve invasion (n=1). Nonirradiated melanomas demonstrated no trace immunoreactivity for neurotrophic factor receptors, whereas irradiated melanomas showed more prominent (trace to moderate) immunoreactivity. When controlled for irradiation, no difference in immunoreactivity for neurotrophin receptors nor tumor duration was observed between retinoinvasive and nonretinoinvasive melanomas. This study failed to demonstrate a direct causation between the expression of neurotrophin receptors and a retinoinvasive uveal melanoma growth pattern.

Initial PET/CT staging for choroidal melanoma: AJCC correlation and second nonocular primaries in 333 patients.

PURPOSE: To report on whole body positron emission tomography/computed tomography (PET/CT) screening for metastasis at diagnosis of primary uveal melanoma. METHODS: Since August 2003, 333 consecutive patients were diagnosed with uveal melanoma and underwent whole body screening for metastatic disease with PET/CT along with liver function tests and physical examination. Abnormal findings prompted further biopsies, blood tests, imaging, or clinical evaluations for confirmation. The presence of metastatic disease and second cancers were evaluated. RESULTS: Using the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) 7th edition criteria, 104 tumors were classified T1 (31%), 162 T2 (49%), 37 T3 (11%), and 30 T4 (9%). Seven of 333 (2.1%; 95% confidence interval [CI] 0.8-4.3) patients had metastatic melanoma. One tumor was a T3 and 6 were T4. Thus, 3% of T3 and 20% of T4 melanomas were found to have metastases at the time of initial diagnosis. Ten patients (3.3%; 95% CI 0.9-5.5) had synchronous second cancers and 28 (8.4%) concurrent benign lesions. The most common metastatic sites were liver (7/7) and bone (2/7). DISCUSSION: This study suggests that PET/CT improves the yield of detecting both extrahepatic metastases, especially from tumors defined as AJCC-T4, and synchronous primary cancers, irrespective of the size of the uveal melanoma. With respect to liver metastases, PET/CT demonstrated high sensitivity and positive predictive values, indicating an overall better performance than conventional screening procedures.