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This paper examines the financial and operational hedging activities of US pharmaceutical and biotech firms that are subject to a high level of information asymmetry stemming from R&D investments during 2001-2006. We find evidence in support of the information asymmetry hypothesis à la Froot, Scharfstein and Stein (1993) that hedging helps mitigate the under-investment problem. Specifically, we find that the use of financial derivatives is associated with greater firm value and that the value enhancement is larger for firms subject to greater information asymmetry and better growth opportunities. There is a synergy between financial hedging and operational hedging where the latter is used to counter product development risk. The results are robust with respect to alternative performance measures, industry-specific growth measures, and the endogeneity problem. Our work is differentiated from existing studies that examined commodity-based industries without addressing information asymmetry. [ABSTRACT FROM AUTHOR]

Purpose: To determine trends in incidence, treatment, and survival with primary uveal melanoma in the United States over a 36-year period from 1973 to 2008. Design: Systematic review of existing databases. Participants: A total of 4070 patients with primary uveal melanoma (International Classification of Disease for Oncology [ICD-O-2] codes C69.3 [choroid], C69.4 [ciliary body and iris], and C69.2 [retina]) derived from the Surveillance, Epidemiology, and End Results (SEER) program database in the United States from 1973 to 2008. Methods: The significance of trends in age-adjusted incidence, treatment, and 5-year relative survival rates were determined using chi-square testing and 95% confidence intervals (CIs). Main Outcome Measures: Age-adjusted incidence, form of treatment (surgery, radiation, or both), and 5-year relative survival rates. Results: There were 4070 cases of uveal melanoma representing 3.1% of all recorded cases of melanoma. The majority of cases (98.3%) were reported by hospital inpatient/outpatient clinics. Histopathologic confirmation was available in 2804 cases (72.1% for all years). The mean age-adjusted incidence of uveal melanoma in the United States was 5.1 per million (95% CI, 4.8–5.3). The majority of cases (97.8%) occurred in the white population. There was a statistically significant variation of age-adjusted incidence between sexes (male = 5.8, 95% CI, 5.5–6.2; and female = 4.4, 95% CI, 4.2–4.7). A decreasing trend was observed in patients treated with surgery alone (93.8% for 1973–1975 vs. 28.3% for 2006–2008), whereas a corresponding increase was seen in those treated with radiation (1.8% for 1973–1975 vs. 62.5% for 2006–2008). No change in the 5-year relative survival rate (81.6%) was observed from 1973 to 2008. Conclusions: The age-adjusted incidence of uveal melanoma (5.1 per million) has remained unchanged from 1973 to 2008. Despite a shift toward more conservative treatments, survival has not improved during this time period. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

The article presents cases on intraocular lymphoma. Intraocular lymphoma is considered as an uncommon intraocular malignant neoplasm that includes primary intraocular lymphoma (PIOL) and metastatic intraocular lymphoma. The incidence of primary central nervous system lymphoma (PCNSL) increased by 0.027 in 1973 to 0.075 in 1983, based on the report released by the National Cancer Institute Surveillance, Epidemiology and End Results (SEER).

: PurposeTo determine variations in 5-year relative survival rates with primary uveal melanoma in the United States over a 25-year period from 1973 to 1997.: DesignSystematic review of existing databases.: ParticipantsTwo thousand four hundred ninety-three patients with primary uveal melanoma, International Classification of Oncology [ICDO-2] codes C69.3 [choroid melanoma] and C69.4 [ciliary body and iris]) derived from Surveillance, Epidemiology, and End Results (SEER) program database in the United States from 1973 to 1997.: MethodsThe patients were stratified according to the treatment (surgery or radiotherapy). The relative 5-year survival was calculated for 2054 patients diagnosed between 1973 and 1993 by the life table method using US life expectancy tables.: Main outcome measuresThe relative 5-year survival rate.: ResultsSurgical treatment was performed in 1476 (72%) cases, and radiotherapy was given in 300 (15%) cases. The proportion of cases treated by radiotherapy increased progressively from 2% to 28% in 20 years. Relative 5-year survival rates ranged from 77% to 84% without a statistically significant variation.: ConclusionsAdvances made in the local methods of treatment of primary uveal melanoma have not led to an improvement in survival. Systemic approaches to management of uveal melanoma are warranted. [Copyright &y& Elsevier]

: PurposeTo determine the incidence of primary uveal melanoma in the United States over a 25-year period from 1973 to 1997.: DesignSystematic review of existing databases.: ParticipantsTwo thousand four hundred ninety-three patients with primary uveal melanoma (International Classification of Oncology [ICDO-2] codes C69.3 [choroid melanoma] and C69.4 [ciliary body and iris]) derived from the Surveillance, Epidemiology, and End Results (SEER) program database in the United States from 1973 to 1997.: MethodsThe significance of trend in age-adjusted incidence rate was determined using chi-square test, and 95% confidence intervals were calculated.: Main outcome measuresThe age-adjusted incidence rate.: ResultsThere was a total of 2493 cases of uveal melanoma, representing 2.9% of all recorded cases of melanoma. Almost all cases (99.4%) were reported by the hospitals, and histopathologic confirmation was available in 81.3% of cases. The mean age-adjusted incidence of uveal melanoma in the United States was 4.3 per million (4.1–4.5; 95% confidence interval [CI]). Most cases (97.8%) occurred in the white population. There was significant variation of incidence between genders (males, 4.9 [4.6–5.2] 95% CI interval; females, 3.7 [3.5–3.9] 95% CI interval). There was no significant variation of incidence by the geographic location of the registry and over the entire period of observation (chi-square test).: ConclusionsThe mean age-adjusted incidence of uveal melanoma (4.3 per million) in the United States is similar to that reported from European countries. The age-adjusted incidence rate of uveal melanoma has remained stable for the past 25 years. [Copyright &y& Elsevier]

Congenital hypertrophy of the retinal pigment epithelium (CHRPE), traditionally regarded as a benign stationary condition, has recently been shown in 5 cases to give rise to an elevated, solid tumor. However, the histopathologic nature of the tumor that arises from CHRPE has not been previously determined. A 65-year-old woman developed a progressively enlarging peripheral fundus tumor that arose from a focus of classic CHRPE. The tumor produced a localized exudative retinal detachment, cystoid macular edema, and surface-wrinkling retinopathy. The mass was removed by local resection, and histopathologic examination revealed a low-grade adenocarcinoma of the retinal pigment epithelium, apparently arising from CHRPE. Although CHRPE is usually a benign nonprogressive lesion, it can give rise to a malignant tumor. Congenital hypertrophy of the retinal pigment epithelium should be observed periodically for development of a neoplasm. [ABSTRACT FROM AUTHOR]

The incidence of melanoma is rising in the United States, leading to an estimated 68,720 new diagnoses and 8,650 deaths annually. The natural history involves metastases to lymph nodes, lung, liver, brain, and often to other sites. Primary treatment for melanoma is surgical excision of the primary tumor and affected lymph nodes. The role of adjuvant or definitive radiation therapy in the treatment of melanoma remains controversial, because melanoma has traditionally been viewed as a prototypical radioresistant cancer. However, recent studies suggest that under certain clinical circumstances, there may be a significant role for radiation therapy in melanoma treatment. Stereotactic radiosurgery for brain metastases has shown effective local control. High dose per fraction radiation therapy has been associated with a lower rate of locoregional recurrence of sinonasal melanoma. Plaque brachytherapy has evolved into a promising alternative to enucleation at the expense of moderate reduction in visual acuity. Adjuvant radiation therapy following lymphadenectomy in node-positive melanoma prevents local and regional recurrence. The newer clinical data along with emerging radiobiological data indicate that radiotherapy is likely to play a greater role in melanoma management and should be considered as a treatment option. [ABSTRACT FROM AUTHOR]

Purpose: The long-term survival of uveal melanoma patients in the US is not known. We compared long-term survival estimates using relative survival, excess absolute risk (EAR), Kaplan-Meier (KM), and competing risk analyses., Setting: Population based cohort study., Study Population: Pooled databases from Surveillance, Epidemiology, and End Results data (SEER, SEER-9+SEER-13+SEER-18)., Main Outcome Measure: Overall Survival (OS), Metastasis Free Survival (MFS) and relative survival, computed directly or estimated via a model fitted to excess mortality., Results: There were 10678 cases of uveal melanoma spanning a period of 42 years (1975-2016). The median age at diagnosis was 63 years (range 3-99). Over half the patients were still alive at the end of 2016 (53%, 5625). The KM estimates of MFS were 0.729 (0.719, 0.74), 0.648 (0.633, 0.663), and 0.616 (0.596, 0.636) at 10, 20, and 30 years, respectively. The cumulative probabilities of melanoma metastatic death at 10, 20 and 30 years were 0.241 (0.236, 0.245), 0.289 (0.283, 0.294), and 0.301 (0.295, 0.307). In the first 5 years since diagnosis of uveal melanoma, the proportion of deaths attributable to uveal melanoma were 1.3 with rapid fall after 10 years. Death due to melanoma were rare beyond 20 years. Relative survival (RS) plateaued to ~60% across 20 to 30 years. EAR parametric modeling yielded a survival probability of 57%., Conclusions: Relative survival methods can be used to estimate long term survival of uveal melanoma patients without knowing the exact cause of death. RS and EAR provide more realistic estimates as they compare the survival to that of a normal matched population. Death due to melanoma were rare beyond 20 years with normal life expectancy reached at 25 years after primary therapy., Competing Interests: We have no competing interests.

Importance: The extent to which uveal melanoma is cured by ocular therapy is not known., Objective: To estimate cured fractions (CF) of uveal melanoma using combination of institutional and Surveillance, Epidemiology, and End Results (SEER) data., Design, Setting, and Participants: Integrative analysis of 42 years of SEER data (1975-2016) with 25 years (1993-2018) of complementary institutional data. The analysis included SEER US patients and molecularly prognosticated patients in the United States and Europe. Three SEER databases (SEER-9, SEER-13, and SEER-18) were merged. A total of 10 678 SEER cases of uveal melanoma diagnosed from 1975 to 2016 using International Classification of Disease for Oncology morphology codes 8720-8790 (for melanoma) and site codes C69.2-4 (for choroid, ciliary body, and iris) were downloaded April 16, 2019. The institutional data included 5 institutional cohorts of 788 molecularly prognosticated patients (diagnosed prior to July 2019) with 3115 person-years at risk of death and 262 observed deaths., Main Outcomes and Measures: Excess absolute risks of death (EAR) and cured fraction (CF) indicates lifetime area under the EAR curve. These are applied to populations and subpopulations., Results: The SEER EAR, with sexes and races pooled, can be modeled as a sum of 2 waves. The first wave peaks at approximately 3 years and is negligible by 15 years, at which time the second wave peaks. Institutional data suggest that the first wave is owing to BAP1 mutant cases (204 of 355 [57.5%]; 95% CI, 52%-63%) and that the second wave is owing to BAP1 wild-type SF3B1 mutant cases (60 of 355 [17%]; 95% CI, 13%-21%). There is also a third group with a low flat EAR time course (91 of 355 [25.5%]; 95% CI, 21%-30%). The overall statistical CF of 60% is reached by approximately 25 years., Conclusions and Relevance: These findings suggest that the benefits of ocular therapy for curing uveal melanoma may be questionable because statistical cures reflect deaths of poor prognosis cases and survival of good prognosis cases. Changes in uveal melanoma patient management may be needed to improve survival.

Purpose: To characterize treatment patterns, overall survival (OS), and risk of second malignant tumors in patients with retinoblastoma (RB) using the SEER (Surveillance Epidemiology and End Results) dataset., Design: Cohort study., Methods: The SEER dataset was used to identify cases of RB using ICD-03 histology codes. Special permission was granted by the SEER administration to release chemotherapy information for this study (information that is not available in the publically available SEER dataset). Treatment of RB for patients with locoregional disease was characterized as surgical therapy, radiation therapy, chemotherapy, or any form thereof across 4 time periods from 1975 to 2010. Observed-to-expected (O/E) ratios for second malignant neoplasms were calculated with the use of age-specific incidence rates., Results: There were 1452 cases of RB identified from 1975 to 2010, with 48% of patients being male and 30% presenting with bilateral disease. Treatment patterns over time of 1220 patients (84%) with localized disease showed an increase in chemotherapy (± any treatment) from 16.5% to 50.2% and a decrease in surgery (± any treatment) from 96.2% to 88.5% and decrease in radiation from 15.2% to 4.9% from the 1975-1979 time period to the 2000-2010 time period. The 10-year OS was 93.7%, 93.7%, 97.5%, and 97% for increasing time periods (1975-1979, 1980-1989, 1990-1999, 2000-2010, respectively; P = .029). Risk of second malignant neoplasms was highest among patients treated with radiotherapy with O/E ratio of 43 compared to 30 and 5 for chemotherapy and surgery alone, respectively., Conclusion: Treatment trends for RB show an increase in chemotherapy utilization with a decrease in radiation therapy from 1975 to 2010. Second malignant neoplasms occurred mainly in patients treated with radiation therapy. Our series demonstrates improvement in survival in contemporary time periods, which parallels a shift in therapy toward chemotherapy with a decline in radiation therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To estimate the risk of malignant transformation of a choroidal nevus in the white population., Design: Systematic literature review., Methods: A literature review was performed to obtain data on the prevalence of choroidal nevi in the white population. Data from studies that used indirect ophthalmoscopy or otherwise corrected data to include the entire fundus were selected. Only studies reporting on the United States population were included. The number of affected individuals was estimated using 2000 U.S. census data. The estimate of annual incident choroidal melanoma cases in the corresponding age- and race-matched population was calculated using the Surveillance, Epidemiology, and End Result database (1973-2000). Average annual age-specific incidence rates for 1973 to 2000 for each of the 5-year age groups (adjusted for the U.S. 2000 population) were calculated and applied to the corresponding census data. The ratio of numbers of affected individuals with choroidal melanoma and choroidal nevi gave the annual rate of malignant transformation of a choroidal nevus., Main Outcome Measures: Annual rate of malignant transformation of a choroidal nevus in the white population of the U.S., Results: The prevalence of choroidal nevus in the white U.S. population ranged from 4.6% to 7.9%. It was estimated that, on average, 8864625 individuals in the U.S. had a choroidal nevus. The number of individuals with choroidal melanoma in the corresponding age- and race-matched population ranged from 989 to 1008 (mean, 1002). The annual rate of malignant transformation of a choroidal nevus was estimated to be 1 in 8845., Conclusions: If it is assumed that all choroidal melanomas arise from preexisting nevi, then the published data suggest a low rate (1/8845) of malignant transformation of a choroidal nevus in the U.S. white population.

Melanomas of the ocular and adnexal structures comprise approximately 5% of all melanomas. The majority (85%) of ocular melanomas are uveal in origin; primary conjunctival and orbital melanomas are rare. The diagnosis of uveal melanoma is made by clinical examination including indirect ophthalmoscopy and by ancillary studies such as fluorescein angiography and ultrasonography. Metastases to the liver develop within 15 years after the initial diagnosis and treatment in approximately 50% of patients with posterior uveal melanoma; however, clinically evident metastatic disease at the time of initial presentation is uncommon, indicating that there is early subclinical metastasis in most cases.

This review provides a summary of the main objectives, significant design features, and major findings and achievements of the Collaborative Ocular Melanoma Study (COMS). It has been written by two ophthalmic oncologists who were not part of the COMS study group; therefore, it represents an extramural view of the trial to supplement summaries published by the COMS investigators. Because the randomized design of the COMS was unique, no attempt is made to make any comparison with the results of previous non-controlled studies.