Second Primary Neoplasms in Patients With Uveal Melanoma: A SEER Database Analysis




Purpose


To determine the risk of second primary neoplasms (SPNs) in subjects previously diagnosed with uveal melanoma (UM), including an analysis on whether radiotherapy is a risk factor to develop these SPNs.


Design


Retrospective cohort study.


Methods


Using the Surveillance, Epidemiology, and End Results (SEER) 9 database, we identified patients diagnosed with UM as their first malignancy between 1973 and 2011 (n = 3976). We obtained standardized incidence ratios (SIR) and excess absolute risks of SPNs on patients with UM compared to a reference population. Multivariate Cox regression models were used to evaluate the effect of radiotherapy in SPN risk.


Results


Sixteen percent (n = 641) of the patients developed SPNs during a median follow-up of 83 months (range, 1–463 months). This represented an 11% excess risk compared to the reference population, mainly owing to a significantly increased risk of skin melanomas (SIR = 2.93, 95% CI: 2.23–3.78) and kidney tumors (SIR = 1.91, 95% CI: 1.27–2.76), primarily in those diagnosed between 30 and 59 years of age. The occurrence of second UM was also increased (SIR = 16.90, 95% CI: 9.00–28.90), which likely includes recurrences misclassified as a second cancer. Radiotherapy was performed in 39% (n = 1538) of the patients. Multivariate analysis revealed that this treatment was not an independent risk factor for SPNs (hazard ratio = 1.06, 95% CI: 0.88–1.26, P = .54).


Conclusions


Patients with UM presented an 11% higher risk of SPNs compared to the reference population. Radiotherapy does not seem to be a risk factor. SPNs should be considered in the surveillance of UM.


Published data on survival of uveal melanoma demonstrate that more than half of the patients are long-term survivors. At 5 and 10 years, the survival rates range between 68%–82% and 57%–62%, respectively. It is well established that cancer survivors are especially prone to developing independent second primary neoplasms (SPNs) and that their characteristics vary according to the site of the first primary tumor. This increased risk is recognized to have multifactorial causes. Lifestyle and environmental exposures, such as smoking and alcohol consumption, have been implicated. Additionally, host susceptibility factors, including genetic risk factors, also seem to play a role. Besides the well-established relevance of genetic susceptibility for cancer in general, SPNs can be part of familial cancer predisposition syndromes. Interestingly, one has been recently described for uveal melanoma. Associated with germline BAP1 mutations, it includes a constellation of uveal and cutaneous melanoma, among other tumors.


The relevance of the treatment modalities applied to the first tumor has also been highlighted, in particular for radiation therapy. This is especially important, as radiotherapy is currently the gold-standard treatment for most uveal melanomas. The suggested underlying factors for SPN risk after this treatment include the doses and modalities applied, as well as the volume of tissue irradiated. This risk is most pronounced in the organs within the irradiated fields but has also been described in sites not directly exposed to radiation. A potential explanation includes “bystander response–like phenomena,” through the release of blood cells and mediators from the irradiated fields that can induce genomic instability and cell transformation.


Despite growing knowledge about treatment-induced effects on the occurrence of SPNs in patients with other malignancies, data are insufficient for uveal melanoma. A few population-based studies were published before radiotherapy became the treatment of choice for these tumors, and therefore did not address this question. More recently, the Collaborative Ocular Melanoma Study (COMS) Group reported the occurrence of SPN in patients treated for choroidal melanoma, characterizing the time to occurrence of SPN and the most frequently affected sites. However, no data from the general population were included.


We present a population-based study that aimed to evaluate whether patients with uveal melanoma demonstrate an increased incidence of SPNs compared to the general population, including an analysis on whether radiation therapy is associated with a higher risk of these SPNs.


Methods


Study Population


This retrospective cohort study followed a group of patients with a diagnosis of uveal melanoma as their first malignancy, who were identified in the Surveillance, Epidemiology, and End Results (SEER) 9 database from 1973 to 2011. The SEER program collects data on all persons diagnosed with cancer residing in several geographically defined regions—the SEER 9 database includes 9 registries, covering approximately 10% of the United States (US) population and being comparable to the US general population, with a case ascertainment rate of 98%. Despite including fewer registries than the newer SEER databases, SEER 9 is the only one that provides data from 1973 onwards. This study met the definition of exempt research. As a result, Institutional Review Board approval was not required. The SEER data is considered nonhuman subject research. The data is anonymized. No patient contact is involved in its collection. The collection of SEER data is also exempt from Health Insurance Portability and Accountability Act regulations.


Patient selection was based on the primary site and histologic subtype of the first malignancy, according to the International Classification of Diseases for Oncology, third edition (ICD-O-3), as follows: topography codes C69.2 (retina), C69.3 (ciliary body), and C69.4 (choroid) for uvea; morphology codes 8720.3 to 8774.3 for melanoma. As previously described, most “retinal” melanomas probably represent misclassification of uveal melanoma; thus they were also considered. ICD-O-3 includes the iris in ciliary body topography. Therefore, these cases were not analyzed separately. SPNs were considered as those diagnosed at least 2 months after the uveal melanoma, as defined by the SEER program. We excluded cases where the diagnosis of uveal melanoma was only made by death certificate or autopsy, because they cannot contribute with person-time for SPN assessment. For both primary and SPNs, we selected only cases with malignant behavior. Regarding treatment for the first malignancy, the SEER database includes information on the type of radiotherapy provided (ie, beam radiation, radioactive implants/radioisotopes, combination of both, radiation not specified or unknown). No details are available for the type of beam irradiation applied and for the doses of any of these treatment modalities. Additionally, there are also no data in the SEER database on the type of surgery performed (ie, enucleation or other surgical modalities) for eye malignancies.


Statistical Analysis


We used the SEER*Stat program – MP-SIR session (Surveillance Research Program, National Cancer Institute SEER*Stat software; seer.cancer.gov/seerstat , version 8.1.5) to perform the multiple primary analyses. Person-years at risk were determined starting in the third month after uveal melanoma diagnosis until date of death, last follow-up, SPN diagnosis, or end of 2011, whichever came first. Observed number of cancers corresponded to the actual reported SPN cases. The expected number of SPNs corresponded to those that would develop if the study cohort patients experienced the same rate of occurrence as a reference SEER population, with comparable sex, 5-year age group, race (white/unknown, black, other), site, and calendar year. For this analysis, we used the reference population “Incidence – SEER 9 Regs Research Data, Nov 2013 Sub (1973–2011) <Katrina/Rita Population Adjustment> – Linked To County Attributes – Total U.S., 1969–2012 Counties.” Briefly, this reference population includes all people living in the SEER 9 geographic areas between 1973 and 2011, based on the US Census Bureau’s Population Estimates Program External Web Site Policy, in collaboration with the National Center for Health Statistics, and with support from the NCI through an interagency agreement. Referent rates (for expected cases) represent SEER 9 incidence rates, which are then stratified by age, sex, race, calendar year, and cancer site, according to the characteristics of our cohort of uveal melanoma patients.


Standardized incidence ratios (SIR) were obtained by observed-to-expected ratio and the 95% confidence interval (95% CI) was calculated based on the Poisson distribution. The excess absolute risk of SPN was calculated by subtracting the expected number from the number of observed cases and dividing by the person-years at risk, and corresponded to the additional cancers (beyond the expected amount). It was expressed per 10 000 person-years.


Univariate and multivariate Cox proportional hazards regression models were used to evaluate the effect of radiotherapy on SPN risk. Owing to the small number of nonwhite subjects in our cohort, for these analyses race was coded as a dichotomous variable (white/unknown vs black/other). A secondary analysis investigated the effect of the type of radiotherapy (beam radiation, radioactive implants/radioisotopes) on SPN risk. For this analysis, subjects given a combination of radiotherapy or with unknown type of radiotherapy were excluded. For multivariate analysis, the proportional hazards assumption was tested using the log minus log curve {ln[ _ ln ( S )]} and the goodness-of-fit test, and no violation was observed for any of the variables. Stata version 12.1 (StataCorp LP, College Station, Texas, USA) was used for all these Cox analyses. The previous analyses censored all subjects who died at the time of death, but an alternative approach could consider death from uveal melanoma or death from other cause as a competing risk. Therefore, all of the previous multivariate models were refit accounting for competing risks using the stcompet and stcrreg routines in Stata.




Results


Study Population


The study cohort consisted of 3976 patients diagnosed with uveal melanoma as their first malignancy ( Table 1 ). Most cases were coded as malignant melanoma without other histologic specification (n = 2475, 62%). The remaining cases were classified as spindle cell melanoma (n = 768, 19%), epithelioid cell melanoma (n = 192, 5%), mixed epithelioid and spindle cell melanoma (n = 504, 13%), amelanotic melanoma (n = 32, 0.8%), and others (n = 5, 0.1%). The median follow-up time was 83 months, with 62% (n = 2427) of the subjects followed for at least 5 years (range, 1–463 months). Nearly 30% (n = 1168) of the patients died of uveal melanoma and the 5- and 10-year disease-specific survival rates were 80% and 69%, respectively. The global survival rate during the available follow-up was 44% (n = 1740).



Table 1

Demographic and Clinical Characteristics of the Population-based Cohort (n = 3976) of Patients With Uveal Melanoma


























































































































































Radiotherapy
Total Population a
N = 3976
Yes
N = 1538
No
N = 2424
P Value
n (%) n (%) n (%)
Patients who developed SPN b 641 (100) 202 (13.13) 438 (18.07)
Sex
Female 1886 (47.43) 714 (46.42) 1167 (48.14) .29 c
Male 2090 (52.57) 824 (53.58) 1257 (51.86)
Race
White or unknown 3926 (98.74) 1515 (98.50) 2398 (98.93) .13 d
Black 22 (0.55) 10 (0.65) 11 (0.45)
Other 28 (0.70) 13 (0.85) 15 (0.62)
Age at melanoma diagnosis
1–29 years 134 (3.37) 37 (2.41) 97 (4.00) .01* d
30–59 years 1715 (43.13) 685 (44.53) 1023 (42.20)
≥60 years 2127 (53.50) 816 (53.06) 1304 (53.80)
Primary site coding
Choroid 3218 (80.94) 1360 (88.43) 1845 (76.11) <.001* c
Ciliary body 689 (17.33) 149 (9.69) 539 (22.24)
Retina 69 (1.74) 29 (1.89) 40 (1.65)
Laterality
Right 1991 (50.08) 771 (50.13) 1213 (50.04) .41 c
Left 1930 (48.54) 741 (48.18) 1182 (48.76)
Bilateral 1 (0.03) 1 (0.07) 0 (0.00)
Unknown 54 (1.36) 25 (1.63) 29 (1.20)
Diagnostic confirmation e
Clinical/direct visualization only 566 (14.24) 311 (20.22) 254 (10.48) <.001* d
Radiology or other imaging technique 566 (14.24) 301 (19.57) 258 (10.64)
Positive cytology, histology, or microscopy 2802 (70.47) 900 (58.52) 1896 (78.22)
Unknown 42 (1.06) 26 (1.69) 16 (0.66)
Surgery
Yes 2340 (58.85) 209 (13.59) 2127 (87.75) <.001* d
No 1570 (39.49) 1296 (84.27) 266 (10.97)
Unknown 66 (1.66) 33 (2.15) 31 (1.28)

SPN = second primary neoplasm.

Asterisk indicates P < .05.

a Fourteen patients have no data available regarding treatment with radiotherapy.


b For 1 of the patients who developed a SPN, no data are available regarding treatment with radiotherapy.


c χ 2 test.


d Fisher exact test.


e According to SEER database record description, this data item refers to the best method used to confirm the presence of the cancer reported during the entire course of the disease and not necessarily at the time of diagnosis.



Secondary Cancers After Uveal Melanoma


SPN occurred in 641 of the patients with uveal melanoma (16%), within a median time of 75 months (range, 2–425 months). Most (n = 583, 15%) had 1 additional cancer and a few had 2 (n = 57, 1%) or 3 (n = 1, 0.03%) new primaries. SIRs demonstrated that patients with uveal melanoma have a significant 11% excess risk of SPN when compared to the reference population, with an excess absolute risk of 17.28/10 000 person-years. This was mainly owing to a significantly higher risk of tumors of the salivary glands, kidney, and soft tissues, as well as skin melanomas ( Table 2 ). The median age at the time of diagnosis of these SPNs was 77, 67, 81, and 69 years, respectively.



Table 2

Risk of Second Primary Neoplasms in Uveal Melanoma Patients
















































































































































































































































































































Second Cancer Site O O/E 95% CI EAR
All sites 641 1.11 a 1.03–1.20 17.28
All sites excluding second UM 628 1.09 a 1.01–1.18 14.08
Oral cavity and pharynx 11 0.81 0.40–1.45 −0.70
Tongue 1 0.31 0.01–1.73 −0.59
Salivary gland 6 4.26 a 1.56–9.27 1.22
Floor of the mouth, gum, and other location 2 0.59 0.07–2.15 −0.36
Tonsil 1 0.68 0.02–3.78 −0.13
Pharynx 1 0.52 0.01–2.89 −0.25
Hypopharynx 1 0.90 0.02–4.99 −0.03
Digestive system 105 0.89 0.73–1.08 −3.38
Esophagus 5 0.81 0.26–1.89 −0.32
Stomach 6 0.59 0.21–1.27 −1.13
Small intestine 5 2.36 0.77–5.51 0.76
Colon, rectum, and anus 65 0.90 0.69–1.14 −1.98
Liver and biliary tract 9 0.95 0.43–1.80 −0.13
Liver 7 1.44 0.58–2.97 0.57
Gallbladder 1 0.62 0.02–3.48 −0.16
Intra- and extrahepatic bile ducts 1 0.33 0.01–1.83 −0.54
Pancreas 13 0.83 0.44–1.42 −0.70
Peritoneum, omentum, and mesentery 2 3.82 0.46–13.79 0.39
Respiratory system 79 0.84 0.67–1.05 −3.85
Larynx 5 0.94 0.31–2.20 −0.08
Lung, bronchus 74 0.85 0.67–1.06 −3.55
Soft tissue including heart 8 3.04 a 1.31–5.98 1.42
Melanoma of the skin 58 2.93 a 2.23–3.78 10.13
Breast 64 1.00 0.77–1.27 −0.08
Female genital system 35 1.34 0.93–1.86 2.34
Cervix uteri 4 1.75 0.48–4.49 0.46
Corpus and uterus, NOS 20 1.42 0.87–2.19 1.57
Ovary 8 1.06 0.46–2.09 0.12
Vagina 2 4.86 0.59–17.54 0.42
Vulva 1 0.69 0.02–3.85 −0.12
Male genital system 111 1.02 0.84–1.23 0.66
Prostate 110 1.03 0.84–1.24 0.76
Testis 1 1.53 0.04–8.51 0.09
Urinary System 66 1.32 a 1.02–1.68 4.24
Bladder 37 1.09 0.77–1.50 0.82
Kidney 28 2.11 a 1.41–3.06 3.92
Ureter 1 1.04 0.03–5.80 0.01
Eye and orbit – melanoma 13 16.90 a 9.00–28.90 3.25
Brain and other nervous system 8 1.31 0.57–2.58 0.50
Thyroid 10 2.06 0.99–3.78 1.36
Thymus 1 2.25 0.06–12.52 0.15
Lymphatic and hematopoietic diseases 48 1.00 0.74–1.33 −0.01
Lymphoma 18 0.74 0.44–1.17 −1.66
Myeloma 10 1.35 0.65–2.48 0.68
Leukemia 20 1.22 0.75–1.89 0.96
Mesothelioma 2 1.18 0.14–4.27 0.08
Miscellaneous 20 1.41 0.86–2.18 1.58

CI = confidence interval; EAR = excess absolute risk; O = observed number of cases; O/E ratio = observed over expected number of cases; UM = uveal melanoma.

When observed values were equal to 0, expected values were reported. No correction for multiple comparisons was performed for any of the above analyses.

a 95% CI not including the null value (= 1), so P < .05.



A statistically significant increased risk for a second uveal melanoma was also noticed in our study cohort, with 13 cases reported ( Table 3 ) within a median latency time of 7 years (range, 2 months to 27 years). Two of these cases occurred in the fellow eye, 2 months and 7 years later than the first malignancy. Ipsilateral second melanomas were coded as new primaries in 9 patients and in 2 patients data regarding laterality were not available. Most cases of second uveal melanomas (n = 9, 69%) occurred after an initial treatment with radiotherapy. As discussed below, we considered that at least some of these second tumors likely represent misclassified recurrences. Therefore, we recalculated the primary outcomes with these second malignancies excluded. Our results confirmed that patients with uveal melanoma demonstrated an increased risk of SPN for all sites of 1.09 (95% CI: 1.01–1.18), excluding cases coded as a second uveal melanoma ( Table 2 ).



Table 3

Characteristics of Patients With a Second Uveal Melanoma Coded as a New Primary















































































































































































Patient Age First uveal melanoma Second uveal melanoma
Year of Diagnosis Site Code Histology Eye Therapy Year of Diagnosis Site Code Histology Eye
1 57 1973 Choroid Malign. melanoma, NOS OD Radiation, NOS 1980 Choroid Malign. melanoma, NOS OS
2 47 1994 Choroid Malign. melanoma, NOS OD BT 2003 Choroid SCM, NOS OD
3 50 2001 CB Malign. melanoma, NOS OD BR 2009 Choroid Mixed epithelioid and SCM OD
4 69 1991 Choroid Malign. melanoma, NOS NA BR 1995 Choroid Malign. melanoma, NOS OS
5 54 1997 Choroid Malign. melanoma, NOS OD BT 2002 Choroid Mixed epithelioid and SCM OD
6 57 2002 Choroid Malign. melanoma, NOS OD BT 2002 Choroid Malign. melanoma, NOS OS
7 60 2005 Choroid SCM, type B OD Surgery 2006 Eye, NOS Malign. melanoma, NOS OD
8 30 1974 CB Malign. melanoma, NOS OD Surgery 1999 CB Epithelioid cell melanoma OD
9 32 1978 CB Malign. melanoma, NOS OS Surgery 1999 CB Malign. melanoma, NOS NA
10 53 2008 Choroid Malign. melanoma, NOS OS BT 2011 Choroid SCM, type B OS
11 71 1998 Choroid Malign. melanoma, NOS OD BT 2004 Choroid Mixed epithelioid and SCM OD
12 71 2002 Choroid Malign. melanoma, NOS OD BR + BT 2005 Orbit, NOS Mixed epithelioid and SCM OD
13 61 1981 Choroid Mixed epithelioid and SCM OS Surgery 2008 Orbit, NOS Malign. melanoma, NOS OS

BR = beam radiation; BT = brachytherapy; CB = ciliary body; Malign = malignant; NA = nonavailable; NOS = not otherwise specified; OD = right eye; OS = left eye; SCM = spindle cell melanoma.


When evaluating the risk during the follow-up period ( Table 4 ), we observed that the increased risk for salivary gland tumors was only significant within the first 5 years after the diagnosis of uveal melanoma. Kidney tumors occurred more frequently in 2 periods: in the first 5 years of follow-up and later among 10- to 19-year survivors. Skin melanoma risk was increased throughout, and was still significant in 19-year survivors.



Table 4

Risk of Second Primary Neoplasms by Site, According to Time Since the Diagnosis of Uveal Melanoma












































































































Cancer Site Time Since Diagnosis
2–11 Months 1–4 Years 5–9 Years 10–19 Years ≥20 Years
O O/E (95% CI) O O/E (95% CI) O O/E (95% CI) O O/E (95% CI) O O/E (95% CI)
All sites 54 1.29 (0.97–1.68) 203 1.23 a (1.07–1.42) 151 1.06 (0.90–1.25) 175 1.08 (0.93–1.26) 58 0.88 (0.67–1.14)
All sites except UM 52 1.24 (0.93–1.63) 200 1.22 a (1.05–1.40) 147 1.04 (0.87–1.22) 174 1.08 (0.93–1.25) 55 0.84 (0.63–1.09)
Salivary gland 0 (Expected = 0.10) 4 10.16 a (2.77–26.00) 1 2.94 (0.07–16.39) 0 (Expected = 0.40) 1 5.66 (0.14–31.54)
Soft tissue 0 (Expected = 0.19) 3 4.07 (0.84–11.90) 1 1.58 (0.04–8.83) 3 4.07 (0.84–11.88) 1 2.93 (0.07–16.32)
Skin melanoma 6 4.39 a (1.61–9.56) 25 4.59 a (2.97–6.77) 10 2.10 a (1.01–3.86) 14 2.52 a (1.38–4.23) 3 1.12 (0.23–3.27)
Kidney 1 1.06 (0.03–5.90) 11 2.95 a (1.47–5.27) 6 1.85 (0.68–4.02) 9 2.44 a (1.12–4.63) 1 0.62 (0.02-3.43)
Eye/orbit melanoma 2 32.56 a (3.94–117.61) 3 12.88 a (2.66–37.63) 4 21.12 a (5.76–54.09) 1 4.91 (0.12–27.35) 3 36.72 a (7.57–107.32)

CI = confidence interval; O = observed number of cases; O/E ratio = observed over expected number of cases; UM = uveal melanoma.

Only sites with significantly higher standardized incidence rates for patients with uveal melanoma are presented.

When observed values were equal to 0, expected values were reported. No correction for multiple comparisons was performed for any of the above analyses.

a 95% CI not including the null value (= 1), so P < .05.



Considering the relevance of age and sex for cancer in general, we additionally evaluated SIRs stratified by these parameters. Our results revealed that subjects aged 30–59 years at the time of diagnosis of uveal melanoma presented the higher risk of developing SPN (for all sites, SIR = 1.18; 95% CI: 1.04–1.34). Interestingly, those diagnosed before that age did not present a significantly increased risk compared to the reference population ( Table 5 ). Regarding sex, compared to the female reference population, women with a previous uveal melanoma presented a 17% significantly increased risk of all sites SPN (95% CI: 1.04–1.32, Table 6 ). There was a trend towards an increased risk for men (7%), but it was not significant. For both sexes, the described significantly higher risk of skin melanoma and kidney tumors was still observed.



Table 5

Risk of Second Primary Neoplasms in Uveal Melanoma Patients, by Age Category at Diagnosis








































































































































Second cancer site Age at Diagnosis of Uveal Melanoma
<30 Years 30–59 Years ≥60 Years
O O/E 95% CI EAR O O/E 95% CI EAR O O/E 95% CI EAR
All sites 5 1.16 0.36–2.72 3.22 254 1.18 a 1.04–1.34 19.80 382 1.07 0.97–1.18 16.04
All sites excluding second UM 5 1.17 0.38–2.72 3.27 246 1.15 a 1.01–1.30 15.98 377 1.06 0.95–1.17 13.16
Salivary gland 0 0.00 0.00–241.97 −0.07 2 3.81 0.46–13.76 0.74 4 4.60 a 1.25–11.79 2.02
Soft tissue including Heart 0 0.00 0.00–86.95 −0.19 2 1.93 0.23–6.96 0.48 6 3.86 a 1.42–8.39 2.86
Skin melanoma 1 2.40 0.06–13.37 2.66 27 2.95 a 1.95–4.29 8.94 30 2.93 a 1.97–4.18 12.72
Kidney 0 0.00 0.00–31.14 −0.54 14 2.43 a 1.33–4.09 4.13 14 1.90 a 1.04–3.19 4.27
Eye and Orbit-Melanoma 0 0.00 0.00–404.39 −0.04 8 24.05 a 10.38–47.39 3.84 5 11.70 a 3.80–27.30 2.95
Miscellaneous b 0 0.00 0.00–82.47 −0.20 4 1.02 0.28–2.61 0.04 16 1.57 0.90–2.54 3.72

CI = confidence interval; EAR = excess absolute risk; O = observed number of cases; O/E ratio = observed over expected number of cases; UM = uveal melanoma.

Only sites with significantly higher standardized incidence rates for patients with uveal melanoma are presented.

When observed values were equal to 0, expected values were reported. No correction for multiple comparisons was performed for any of the above analyses.

a 95% confidence interval not including the null value (= 1), so P < .05.


b Miscellaneous represents all site and histologic combinations not covered in the remaining groups provided by the SEER database (all data and codes available at seer.cancer.gov/siterecode_b/icdo3_who2008/ ).



Table 6

Risk of Second Primary Neoplasms in Uveal Melanoma Patients, by Sex



































































































Second cancer site Sex
Male Female
O O/E 95% CI EAR O O/E 95% CI EAR
All sites 375 1.07 0.97–1.19 13.08 266 1.17 a 1.04–1.32 21.84
All sites excluding second UM 366 1.05 0.94–1.16 8.78 262 1.16 a 1.02–1.31 19.82
Salivary gland 3 3.17 0.65–9.26 1.05 3 6.49 a 1.34–18.97 1.40
Soft tissue including heart 5 3.07 1.00–7.16 1.72 3 2.98 0.61–8.70 1.10
Skin melanoma 27 2.00 a 1.32–2.91 6.89 31 4.90 a 3.33–6.96 13.65
Kidney 17 1.87 a 1.09–3.00 4.04 11 2.64 a 1.32–4.72 3.78
Eye and orbit melanoma 9 19.83 a 9.11–37.83 4.36 4 12.60 a 3.43–32.25 2.04
Miscellaneous b 7 0.91 0.37–1.88 −0.35 13 2.00 a 1.07–3.42 3.60

CI = confidence interval; EAR = excess absolute risk; O = observed number of cases; O/E ratio = observed over expected number of cases; UM = uveal melanoma.

Only sites with significantly higher standardized incidence rates for patients with uveal melanoma are presented.

When observed values were equal to 0, expected values were reported. No correction for multiple comparisons was performed for any of the above analyses.

a 95% CI not including the null value (= 1), so P < .05.


b Miscellaneous represents all site and histologic combinations not covered in the remaining groups provided by the SEER database (all data and codes available at seer.cancer.gov/siterecode_b/icdo3_who2008/ ).

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Jan 6, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Second Primary Neoplasms in Patients With Uveal Melanoma: A SEER Database Analysis

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