Pregnancy and Plaque Brachytherapy Treatment of Uveal Melanoma：A Retrospective Study

Pregnancy and Plaque Brachytherapy Treatment of Uveal Melanoma：A Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pregnancy and Plaque Brachytherapy Treatment of Uveal Melanoma：A Retrospective Study Hao-Tian Wu, Yue-Ming Liu, Li Dong, Rui-Heng Zhang, Wen-Da Zhou, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3094982/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Sep, 2024 Read the published version in BMC Ophthalmology → Version 1 posted 9 You are reading this latest preprint version Abstract Background To examine whether pregnancy affects the prognosis of uveal melanoma (UM) patients undergoing plaque brachytherapy (PBT) and if PBT has any effect on the outcome of such pregnancy. Methods We conducted a single-center retrospective study at the Beijing Tongren Hospital on the population of women with childbearing age who were diagnosed with uveal melanoma and underwent iodine-125 plaque brachytherapy. The outcome of each pregnancy and the status of the fetus was followed-up. Survival analysis were performed using Kaplan-Meier method, with the metastasis and death as endpoints. Results 13 patients with 13 full-term pregnancies and 96 non-pregnant women with matched age and tumor size were included. In pregnant group, two patients developed metastasis, one of which died shortly after delivery; local recurrence of UM occurred in 2 patients after or during delivery, and 2 other patients developed secondary glaucoma due to radiation retinopathy. None of the other pregnant patients reported any signs of disease progression. In the control group, 18 metastasis cases including 12 deaths were documented. Pregnant patients and matched control subjects showed no statistical difference in both Metastasis-free survival (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.15–2.86; P = 0.576) and overall survival (HR: 0.48, 95% CI: 0.06–3.66; P = 0.464). All pregnant patients carried the pregnancy to term and delivered healthy babies with no report of placental or infant metastases to date. Conclusion Pregnancy exerted no adverse effects on the prognosis of UM patients who receive PBT. While PBT had no significant effect on maternal fertility, and did not show teratogenic effect on the fetus so far, long-term effects require further follow-up studies. Pregnancy Uveal melanoma Plaque brachytherapy Figures Figure 1 Introduction Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults( 1 ), with a 5-year survival rates ranging from 25–66%( 2 ). Most cases may result in poor vision or even enucleation( 3 ). Plaque radiotherapy is a treatment that sutures a curvilinear radioactive plaque onto the sclera, precisely over the tumor, to deliver trans-scleral radiation to the UM. In expert hands and with careful patient selection, plaque radiotherapy can achieve comparable overall life prognosis to other management techniques such as enucleation( 4 , 5 ) with globe salvage in 95% of patients, often with useful vision retention( 3 ). As a result, this treatment has been used as the first line therapy for most UM patients in our hospital. According to multiple reports, melanoma is more commonly seen in the elder, male subjects( 6 , 7 ). However, in clinical practice, a significant number of women of childbearing age (15–45 years old) still face the threat of UM. Also despite the fact that cancer survivors were 27% less likely to give birth than the general population, survivors of non-reproductive organ cancer had practically similar relative birth rates as the background population( 8 ). Therefore, in treating these patients, it is important to take care of their reproduction needs and concerns. There has been conflicting data and opinions on how the physiological process of pregnancy affects UM on the prognosis. Given that pregnancy induces physiological changes in the eye( 9 ), it can be assumed that pregnancy may have an effect on intraocular tumors such as UM. Hartage et.al. found that history of pregnancy had an increased risk of UM( 10 , 11 ) which suggested that female hormones may have some effect on the pathophysiological process of UM. While other authors reported exact opposite findings that a history of pregnancy decreased risk of developing UM( 12 ). For prognosis, multiple researchers found no appreciable influence on that of UM at all( 13 , 14 ) while Egan et.al. believes a history of childbearing affords protection from metastatic death in intraocular melanoma( 15 ). These various findings make the effect of pregnancy on UM an interesting and worthy aspect of study. As for the effect of UM and its treatment on pregnancy, since plaque brachytherapy is a treatment of radiation, though localized and minimal, its impact on maternal fertility and the fetus has become a concern for many patients and clinicians. This study aimed to evaluate the prognosis of women of childbearing age who received plaque brachytherapy in our hospital, and the outcomes of their pregnancy. Materials and Methods A single-center retrospective study was performed on the medical records of clinically diagnosed UM patients who were of childbearing age and treated with iodine-125 plaque brachytherapy by one physician (Dr. Yue-Ming Liu) at Beijing Tongren Hospital, Capital Medical University between January 1, 2012 and December 31, 2019. This study was approved by the ethical committee of Beijing Tongren Hospital of Capital Medical University. Research adhered to the tenets of the Declaration of Helsinki. All adult subjects (Age ≥ 18 years old) involved in the clinical data used in this study signed written informed consent. The informed consent of subjects who were less than 18 years old was signed by their guardian. The patients were diagnosed with UM using ophthalmoscopy, ultrasonography, and fundus fluorescein angiography, and were all immediately treated by plaque brachytherapy (PBT). The size of the plaques was designed by the nuclear medicine department of Beijing Tongren hospital according to the maximum tumor base diameter of each patient. Then the device was placed precisely on the sclera over the tumor via surgery. The prescription dose at the top of the tumor was 100Gy, and the time to reach the prescription dose could be calculated according to the activity of the plaque and the height of the tumor. When the prescription dose was reached, the device was removed. All patients were evaluated at regular intervals after PBT treatment and were followed up until Oct. 2021. Since none of the patients gave birth at Tongren hospital, the outcome of each pregnancy and the status of the fetus was followed-up through physicians of birth hospital. The clinical data of 282 consecutive childbearing-age female patient including age, gender, date of treatment was collected. Tumor diameter was measured by B-scan ultrasonography. For pregnant patients, the date of delivery, pre-pregnancy and post-pregnancy clinical features of the tumor and disease related events, if any, were carefully documented. Since all pregnancies were carried to term, date of conception was estimated 40weeks before delivery. A total of 13 women had 13 full-term pregnancies after the diagnosis and PBT treatment of uveal melanoma. Since age is an independent prognostic factor for metastases of UM, and number of subjects did not permit formal multivariate analyses that would adjust for this age discrepancy, we selected non-pregnant women who were of comparable age and who had similar tumor base diameter and tumor height as control subjects. Selections were made without knowledge of the survival status of the patient. We used a commercially available statistical analysis program (SPSS 25.0; IBM-SPSS Inc., Chicago, IL, USA) for the statistical analysis of the data. The statistical significance of differences between the pregnant group and the control group was calculated using independent-sample t test and chi-square test. Analysis-survival comparisons were based on the Kaplan-Meier method, with the endpoint being diagnosis of metastases and death. There were no deaths due to other causes. Comparability of survival distributions was evaluated using the log-rank test. Results Demographics of patients Ultimately, a total of 109 patients were included in our study with a median age of 32 years old (range: 15–38 years old), including 13 patients who had pregnancy after PBT treatment of UM (pregnant group, median age 30, range 24–38) and 96 patients who met our criteria as control group (median age 33 range 15–37). For all included patients, the height of the tumors was between 2.4 mm and 14.6 mm (mean: 7.1 ± 2.2). The mean tumor basal diameter was 13.0 ± 2.9 mm (5.7 mm-20.7 mm) (Table 1 ). There was no difference in onset age (median, 33 and 30 years old, respectively; P = 0.391), tumor base diameter (mean, 13.1 ± 2.8 and 12.8 ± 3.5 mm, respectively; P = 0.176), or tumor height (mean, 7.1 ± 2.2 and 7.4 ± 2.9 mm, respectively; P = 0.416) between the two groups. The clinical features and pregnancy outcomes of pregnant patients were shown in Table 2 . Table 1 Basic characteristics of included patients. Pregnant group (n = 13) Non-pregnant group (n = 96) P value Mean Age 30 31 0.391 Max 38 38 Min 24 15 Tumor Base 12.8 ± 3.5 13.1 ± 2.8 0.176 Tumor Height 7.4 ± 2.9 7.1 ± 2.2 0.416 Metastasis case (%) 2(15.38%) 18(18.75%) 0.769 Death case(%) 1(7.69%) 12(12.5%) 0.616 Table 2 Clinical features and pregnancy outcomes of pregnant patients after PBT (n = 13). Case No. Age at Diagnosis Clinical Features in Primary Survey Time of PBT Pre-Pregnancy Clinical Features Date of Dilivery Post-Pregnancy Clinical Features Outcome Base height Base height Base height 1 30 17.0 10.0 2016/10/10 15.8 5.6 2020/2/1 15.8 4.2 Alive 2 28 11.3 5.0 2014/9/22 8.4 3.3 2019/9/1 NA Alive 3 37 11.3 8.9 2015/4/20 13.0 7.5 2018/3/1 12.9 6.6 Discovered metastasis on 2018/1/1, Dead on 2018/4/1 4 30 19.4 4.4 2019/3/11 12.0 3.6 2020/8/1 NA Enucleation during pregnancy 5 25 11.4 8.1 2012/3/8 12.0 5.7 2016/12/1 11.6 3.7 Alive 6 31 10.6 6.0 2015/2/2 8.4 6.1 2016/4/1 9.3 3.8 Alive 7 26 11.3 7.7 2013/11/27 NA 2020/9/1 NA Enucleation in 2014 8 34 17.0 14.6 2016/6/6 NA 2020/5/1 NA Enucleation in 2017/2 9 32 12.4 6.4 2015/3/23 9.0 3.9 2016/10/1 8.4 3.2 Alive 10 38 7.5 4.9 2015/5/18 7.1 4.2 2018/4/1 7.3 2.8 Alive 11 25 14.7 7.5 2018/3/19 11.9 5.5 2020/10/1 11.2 4.8 Alive 12 26 14.5 8.6 2013/11/6 20.7 8.6 2017/12/1 NA Enucleation after delivery(tumor body filled vitreous chamber) Discovered metastasis on 2018/1/31 13 24 8.1 4.1 2013/3/1 6.4 0.9 2017/4/1 NA Alive Patient outcome The mean follow-up time was 67.0 ± 27.7 months (median:66.0 months, range:21.0 to 116.0 months). In 20 patients, metastasis had developed by the close of the study; metastatic disease was diagnosed in one woman 2 months after the birth of a child, 50 months after treatment; metastasis developed in one woman during pregnancy, and the patient died 1 month after delivery; in 18 women, with no pregnancies after diagnosis, metastases developed between 5 months and 6.8 years (median, 3.1 years) after treatment, unfortunately, twelve of which died. In the pregnant group, local recurrence of choroidal melanoma occurred in 2 patients after or during delivery, and 2 other patients developed secondary glaucoma due to radiation retinopathy. These 4 patients were treated by enucleation immediately or after delivery. Enucleation and pathology examination were conducted at local hospital or our own. All pathology result confirmed the diagnosis of uveal melanoma and revealed necrosis of most of the tumor tissue. None of the other pregnant patients who had examination before and after pregnancy (n = 7) showed rapid tumor growth or other signs of disease progression. Local tumor recurrence, enucleation and pathological data of the control group were absent from the research. Surviving women in the study were followed an average of 5.3 years after diagnosis (range, 1.8 years to 9.7 years) and the follow-up pregnancy ranged were from 7 months to 11.1 years (mean, 4.6 years). Thirteen deaths were documented and were all caused by metastatic melanoma. Metastasis and death rate of the two groups pregnant / non-pregnant were 15.38% / 18.75% and 7.69% / 12.5%, respectively. Results among the two groups (pregnant v.s. non-pregnant) showed no statistical significance of metastasis ( P = 0.77) and death ( P = 0.62). Given the small sample size of patients who got pregnant, metastasis-free survival rate and survival rate may not reflect true characteristics of the two groups. We compared Metastasis-free survival months and overall survival months of both groups using Kaplan-Meier method (Fig. 1 ). Pregnant patients and matched control subjects showed no statistical difference in both aspects (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.15–2.86, P = 0.576 and HR: 0.48, 95% CI: 0.06–3.66; P = 0.464). Pregnancy All 13 patients in the pregnant group began their pregnancy some time (median: 31 months, range: 3 to 71 months) after PBT treatment. All pregnancies were conceived naturally and were carried to term without any report of adverse events. All pregnant patients delivered healthy babies and with no report of placenta or infant metastases. Discussion This is the first study to focus on the impact of pregnancy on the prognosis of UM patients treated with PBT and that based on Chinese population. Also, we were the first to discuss weather UM or PBT treatment has any effect on the physiology process of pregnancy and its outcome. Above all, our results show that the survival and metastasis rates of these patients is similar to that of women of childbearing age who had no pregnancy after treatment. This result is consistent with the absence of estrogens and progestogens in UMs( 11 , 16 – 18 ). The only two previous clinical studies( 13 , 14 ) which focused on pregnancy occurred after the treatment of UM also supports our findings. Similar to our report, both studies treated most their patients with conservative treatment primarily such as proton beam irradiation or brachytherapy. Therefore, These findings of similar prognosis among patients who had or didn’t have children after PBT may also be the result of the cessation of mitotic activity and tumor cell necrosis in most patients after local radiotherapy( 19 ). However, there have been occasional cases of significantly increased UM during pregnancy over the past few decades( 16 , 17 ). Lee et.al reported a 31-year-old woman with a 29-week pregnancy was diagnosed with uveal melanoma( 17 ). She refused any treatment for the remaining three months of her pregnancy and the tumor increased in size from 8×5 mm 2 to 13×12 mm 2 . Recently, Yue et.al. reported the first Chinese case of accelerate growth of UM during pregnancy and the tumor showed a rapid growth rate and extended to the orbit with muscle invasion. Similar to the previous case, the patient did not receive any treatment before the end of pregnancy, also there was no detailed medical report but only the subjective feelings of the patient prior to pregnancy. Combining previous retrospective case-control studies and reports of these two cases, we suggest that UM patients treated with local radiation therapy is probably unaffected by hormonal and ocular physiological changes during pregnancy. Also, similar to some previous studies, we demonstrated that UM had no significant impact on maternal fertility for there had been hundreds of cases reported of UM discovered during pregnant and UM patients getting pregnant( 11 , 14 , 16 , 20 – 22 ). Among all these reports, including our own, and the vast number of cases that they have reported, we found only one case report of placental metastasis attributed to choroidal melanoma( 23 ), and none fetal metastasis. Therefore, we can draw a preliminary conclusion that it is extremely unlikely for choroidal melanoma to metastasize to fetus. Additionally, we also proved that the plaque brachytherapy with localized radiation also has neither significant effect on maternal fertility, nor teratogenic effect on the fetus. Some limitations of this study should be also noted. First of all, like previous studies, the number of pregnant cases in this study was limited. UM is a rare disease with most patients presenting between the ages of 50 years and 70 years( 1 ). It is estimated to have an incidence rate of four to eight per million, with a reported higher rate among men( 2 , 24 ). Therefore, few women of childbearing age have a history of uveal melanoma. Additionally, although survivors of non-reproductive organ cancer had similar birth rates as the background population( 8 ), in clinical practice, many patients gave up the idea of having children upon diagnosis of malignant tumor. These factors have limited the number of cases in studies of pregnancy in UM patients after treatment. Secondly, according to follow-up, gross examination of the placenta did not show any evidence of metastatic disease, and since none of the pregnant patients gave birth in our hospital, none of the specimen underwent microscopic examination. We believe that pathological examination of the placenta should be performed as described by previous study( 23 ) to accurately exclude placental metastases. In the past 20 years, few articles have focused on this issue, and we hope to attract researchers' attention to women of reproductive age with malignant tumors. Further clinical and basic studies are needed to draw more definitive conclusions. Conclusions Despite these controversies and limitations, the results of this study are a great piece of good news for UM patients with fertility needs, and also provide valuable reference for clinicians to provide fertility guidance to UM patients. We demonstrated that the prognosis of women with uveal melanoma who underwent PBT is not influenced by pregnancy. Also, plaque brachytherapy had no significant effect on maternal fertility, and did not show teratogenic effect on the fetus so far. Therefore, if a patient conceives after the diagnosis of UM and underwent PBT, pregnancy termination is not necessary, but a close ophthalmological follow-up until delivery and a regular ophthalmologic examination of the baby is strongly advised. Declarations Ethics approval and consent to participate This study was approved by the ethical committee of Beijing Tongren Hospital of Capital Medical University. Research adhered to the tenets of the Declaration of Helsinki. All adult subjects (Age≥18 years old) involved in the clinical data used in this study signed written informed consent. The informed consent of subjects who were less than 18 years old was signed by their guardian. Consent for publication Not applicable Availability of data and materials Research data of this study are not publicly available on legal grounds. Data can be made available from the corresponding author on a reasonable request. Declaration of Interests All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding This study was supported by National Natural Science Foundation of China (82141128); The Capital Health Research and Development of Special (2020-1-2052); Science & Technology Project of Beijing Municipal Science & Technology Commission (Z201100005520045, Z181100001818003) Authors' contributions Conception and design of the research: HTW, YML and WBW; Acquisition and interpretation of the data: HTW, YML, WBW and DL, RHZ, WDZ, HYL; Statistical analysis and writing of the manuscript: HTW, YML, DL, RHZ and HYL; Critical revision of the manuscript: HTW and WBW. Acknowledgements Not applicable. References Jager MJ, Shields CL, Cebulla CM, Abdel-Rahman MH, Grossniklaus HE, Stern MH, et al. Uveal melanoma. Nat Rev Dis Primers. 2020;6(1):24. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118(9):1881-5. Shields CL, Shields JA, Cater J, z KGn, Miyamoto C, Micaily B, et al. Plaque Radiotherapy for Uveal Melanoma: Long-term Visual Outcome in 1106 Consecutive Patients. Arch Ophthalmol. 2000(118):1219-28. Diener-West M, Earle JD, Fine SL. The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma, III: Initial Mortality Findings. AMA archives of ophthalmology. 2001(119):969-82. Jampol LM, Moy CS, Murray TG, Reynolds SM, Albert DM, Schachat AP, et al. The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma: IV. Local Treatment Failure and Enucleation in the First 5 Years after Brachytherapy. COMS Report No. 19. Ophthalmology. 2020;127(4S):S148-S57. Singh N, Bergman L, Seregard S, Singh AD. Uveal Melanoma: Epidemiologic Aspect. Springer Berlin Heidelberg. 2014. Kaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. Eye (Lond). 2017;31(2):241-57. Hartman M, Liu J, Czene K, Miao H, Chia KS, Salim A, et al. Birth rates among female cancer survivors: a population-based cohort study in Sweden. Cancer. 2013;119(10):1892-9. Naderan M. Ocular changes during pregnancy. J Curr Ophthalmol. 2018;30(3):202-10. Hartge P, Tucker MA, Shields JA, Augsburger J, Hoover RN, Joseph F. Fraumeni J. Case-Control Study of Female Hormones and Eye Melanoma. cancer resaearch. 1989(49):4622-5. Zinkhan M, Stang A, Jockel KH, Marr A, Bornfeld N, Schmidt-Pokrzywniak A. Having children, social characteristics, smoking and the risk of uveal melanoma: a case-control study. Ophthalmic Epidemiol. 2013;20(6):360-8. Holly EA, Aston DA, Ahn DK, Kristiansen JJ, Char DH. Uveal Melanoma, Hormonal and Reproductive Factors in Women. cancer resaearch. 1991(51):1370-2. Egan KM, Walsh SM, Seddon JM, Gragoudas ES. An Evaluation of the Influence of Reproductive Factors on the Risk of Metastases from Uveal Melanoma. Ophthalmology. 1993(100):1160-6. Lemaitre S, Levy-Gabriel C, Desjardins L, Plancher C, Asselain B, Vincent-Salomon A, et al. Choroidal melanoma and pregnancy. Acta Ophthalmol. 2016;94(7):e652-e60. Egan KM, Quinn JL, Gragoudas ES. Childbearing History Associated With Improved Survival in Choroidal Melanoma. Arch Ophthalmol. 1999(117):939-42. Seddon JM, Maclaughlin DT, Albert DM, Gragoudas ES, III MF. Uveal melanoma presenting during pregnancy and the investigation of oestrogen receptors in melanomas. British Journal of Ophthalmology. 1982(66):695-704. Lee CS, Yang WI, Shin KJ, Lee SC. Rapid growth of choroidal melanoma during pregnancy. Acta Ophthalmol. 2011;89(3):e290-1. Yue H, Qian J, Ren H, Zhang R, Gan L, Bi YW. Accelerated growth of uveal melanoma related to pregnancy: a case report and literature review. Int J Ophthalmol. 2021;14(2):326-9. Shields CL, Shields JA, Karlsson U, Menduke H, Brady LW. Enucleation after Plague Radiotherapy for Posterior Uveal Melanoma. Ophthalmology. 1990;97(12):1665-70. Shields CL, Shields JA, Jr. RCE, Potter PD, Menduke H. Uveal Melanoma and Pregnancy: A Report of 16 Cases. Ophthalmology. 1991;98(98):1667-73. Miller E, Barnea Y, Gur E, Leshem D, Karin E, Weiss J, et al. Malignant melanoma and pregnancy: second thoughts. J Plast Reconstr Aesthet Surg. 2010;63(7):1163-8. Schmidt-Pokrzywniak A, Kalbitz S, Kuss O, Jöckel K-H, Bornfeld N, Stang A. Assessment of the effect of iris colour and having children on 5-year risk of death after diagnosis of uveal melanoma: a follow-up study. BMC Ophthalmology. 2014;14:42. Marsh RdW, Chu N-M. Placental metastasis from primary ocular melanoma: A case report. Am J Obstet Gynecol. 1996(174):1654-5. Park SJ, Oh CM, Kim BW, Woo SJ, Cho H, Park KH. Nationwide Incidence of Ocular Melanoma in South Korea by Using the National Cancer Registry Database (1999-2011). Invest Ophthalmol Vis Sci. 2015;56(8):4719-24. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Sep, 2024 Read the published version in BMC Ophthalmology → Version 1 posted Editorial decision: Revision requested 27 Jan, 2024 Reviews received at journal 27 Jan, 2024 Reviews received at journal 18 Aug, 2023 Reviewers agreed at journal 10 Aug, 2023 Reviewers invited by journal 10 Jul, 2023 Editor assigned by journal 10 Jul, 2023 Editor invited by journal 04 Jul, 2023 Submission checks completed at journal 04 Jul, 2023 First submitted to journal 22 Jun, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3094982","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":215504670,"identity":"5c83e10a-5e29-455c-adce-d2f17ac54f23","order_by":0,"name":"Hao-Tian Wu","email":"","orcid":"","institution":"Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hao-Tian","middleName":"","lastName":"Wu","suffix":""},{"id":215504671,"identity":"4d7f498d-76b2-475f-be85-2e15ab7f9cb9","order_by":1,"name":"Yue-Ming Liu","email":"","orcid":"","institution":"Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yue-Ming","middleName":"","lastName":"Liu","suffix":""},{"id":215504672,"identity":"390a760b-17c0-4876-9a67-0863ba6124a5","order_by":2,"name":"Li Dong","email":"","orcid":"","institution":"Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Dong","suffix":""},{"id":215504673,"identity":"56fa9cb2-face-4909-a99e-489cdeb02251","order_by":3,"name":"Rui-Heng Zhang","email":"","orcid":"","institution":"Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rui-Heng","middleName":"","lastName":"Zhang","suffix":""},{"id":215504674,"identity":"7db75117-f9ad-498d-aca7-18fa10fce74b","order_by":4,"name":"Wen-Da Zhou","email":"","orcid":"","institution":"Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wen-Da","middleName":"","lastName":"Zhou","suffix":""},{"id":215504675,"identity":"ca2085d0-12a2-4573-845c-3afa3b9d7e54","order_by":5,"name":"He-Yan Li","email":"","orcid":"","institution":"Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"He-Yan","middleName":"","lastName":"Li","suffix":""},{"id":215504676,"identity":"2a30379c-caa4-4dcf-a201-417cb4b6c99b","order_by":6,"name":"Wen-Bin Wei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYFACxgYgcYAHxHqQUFFDihY2BmaDB2eOEW3VAQagFjbJhy3MhNUaHG9uk/i4446MuXzvs4rEBjYG/vbuBPxazhxsk5x55hmPZRu72Y3EHTIMEmfObsCrBais7TZv22Eeg2NsbDcSz7AxGEjkEtBy/2Hb7b9QLQWJbcxEaLnB2HabEaqFgSgt9mcS23/2tj0Dakljlkg4c4yHoF8k248/NvjZdsfe4PAxxo8/Kmrk+Nt78WvBADykKR8Fo2AUjIJRgBUAANX1TNtCHWG5AAAAAElFTkSuQmCC","orcid":"","institution":"Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Wen-Bin","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2023-06-22 07:14:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3094982/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3094982/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12886-024-03681-6","type":"published","date":"2024-09-27T15:57:22+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":39700805,"identity":"f8aad795-86c6-4344-924b-7b9be3046653","added_by":"auto","created_at":"2023-07-07 14:06:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":492217,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curves for the metastasis (A) and overall survival (B) in the two groups.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3094982/v1/2d3e8fd68824c67feb141bf3.png"},{"id":65627183,"identity":"1f3a680c-1f9e-4232-ae2a-ab52043af79b","added_by":"auto","created_at":"2024-09-30 16:13:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":887992,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3094982/v1/aadac951-57c1-4a61-aaa0-2d1727c58620.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pregnancy and Plaque Brachytherapy Treatment of Uveal Melanoma：A Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eUveal melanoma (UM) is the most common primary intraocular malignant tumor in adults(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e), with a 5-year survival rates ranging from 25\u0026ndash;66%(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Most cases may result in poor vision or even enucleation(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Plaque radiotherapy is a treatment that sutures a curvilinear radioactive plaque onto the sclera, precisely over the tumor, to deliver trans-scleral radiation to the UM. In expert hands and with careful patient selection, plaque radiotherapy can achieve comparable overall life prognosis to other management techniques such as enucleation(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) with globe salvage in 95% of patients, often with useful vision retention(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). As a result, this treatment has been used as the first line therapy for most UM patients in our hospital.\u003c/p\u003e \u003cp\u003eAccording to multiple reports, melanoma is more commonly seen in the elder, male subjects(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, in clinical practice, a significant number of women of childbearing age (15\u0026ndash;45 years old) still face the threat of UM. Also despite the fact that cancer survivors were 27% less likely to give birth than the general population, survivors of non-reproductive organ cancer had practically similar relative birth rates as the background population(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Therefore, in treating these patients, it is important to take care of their reproduction needs and concerns.\u003c/p\u003e \u003cp\u003eThere has been conflicting data and opinions on how the physiological process of pregnancy affects UM on the prognosis. Given that pregnancy induces physiological changes in the eye(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), it can be assumed that pregnancy may have an effect on intraocular tumors such as UM. Hartage et.al. found that history of pregnancy had an increased risk of UM(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) which suggested that female hormones may have some effect on the pathophysiological process of UM. While other authors reported exact opposite findings that a history of pregnancy decreased risk of developing UM(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). For prognosis, multiple researchers found no appreciable influence on that of UM at all(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) while Egan et.al. believes a history of childbearing affords protection from metastatic death in intraocular melanoma(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). These various findings make the effect of pregnancy on UM an interesting and worthy aspect of study.\u003c/p\u003e \u003cp\u003eAs for the effect of UM and its treatment on pregnancy, since plaque brachytherapy is a treatment of radiation, though localized and minimal, its impact on maternal fertility and the fetus has become a concern for many patients and clinicians.\u003c/p\u003e \u003cp\u003eThis study aimed to evaluate the prognosis of women of childbearing age who received plaque brachytherapy in our hospital, and the outcomes of their pregnancy.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eA single-center retrospective study was performed on the medical records of clinically diagnosed UM patients who were of childbearing age and treated with iodine-125 plaque brachytherapy by one physician (Dr. Yue-Ming Liu) at Beijing Tongren Hospital, Capital Medical University between January 1, 2012 and December 31, 2019. This study was approved by the ethical committee of Beijing Tongren Hospital of Capital Medical University. Research adhered to the tenets of the Declaration of Helsinki. All adult subjects (Age\u0026thinsp;\u0026ge;\u0026thinsp;18 years old) involved in the clinical data used in this study signed written informed consent. The informed consent of subjects who were less than 18 years old was signed by their guardian.\u003c/p\u003e \u003cp\u003eThe patients were diagnosed with UM using ophthalmoscopy, ultrasonography, and fundus fluorescein angiography, and were all immediately treated by plaque brachytherapy (PBT). The size of the plaques was designed by the nuclear medicine department of Beijing Tongren hospital according to the maximum tumor base diameter of each patient. Then the device was placed precisely on the sclera over the tumor via surgery. The prescription dose at the top of the tumor was 100Gy, and the time to reach the prescription dose could be calculated according to the activity of the plaque and the height of the tumor. When the prescription dose was reached, the device was removed. All patients were evaluated at regular intervals after PBT treatment and were followed up until Oct. 2021. Since none of the patients gave birth at Tongren hospital, the outcome of each pregnancy and the status of the fetus was followed-up through physicians of birth hospital.\u003c/p\u003e \u003cp\u003eThe clinical data of 282 consecutive childbearing-age female patient including age, gender, date of treatment was collected. Tumor diameter was measured by B-scan ultrasonography. For pregnant patients, the date of delivery, pre-pregnancy and post-pregnancy clinical features of the tumor and disease related events, if any, were carefully documented. Since all pregnancies were carried to term, date of conception was estimated 40weeks before delivery. A total of 13 women had 13 full-term pregnancies after the diagnosis and PBT treatment of uveal melanoma. Since age is an independent prognostic factor for metastases of UM, and number of subjects did not permit formal multivariate analyses that would adjust for this age discrepancy, we selected non-pregnant women who were of comparable age and who had similar tumor base diameter and tumor height as control subjects. Selections were made without knowledge of the survival status of the patient.\u003c/p\u003e \u003cp\u003eWe used a commercially available statistical analysis program (SPSS 25.0; IBM-SPSS Inc., Chicago, IL, USA) for the statistical analysis of the data. The statistical significance of differences between the pregnant group and the control group was calculated using independent-sample t test and chi-square test. Analysis-survival comparisons were based on the Kaplan-Meier method, with the endpoint being diagnosis of metastases and death. There were no deaths due to other causes. Comparability of survival distributions was evaluated using the log-rank test.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDemographics of patients\u003c/h2\u003e \u003cp\u003eUltimately, a total of 109 patients were included in our study with a median age of 32 years old (range: 15\u0026ndash;38 years old), including 13 patients who had pregnancy after PBT treatment of UM (pregnant group, median age 30, range 24\u0026ndash;38) and 96 patients who met our criteria as control group (median age 33 range 15\u0026ndash;37). For all included patients, the height of the tumors was between 2.4 mm and 14.6 mm (mean: 7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2). The mean tumor basal diameter was 13.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9 mm (5.7 mm-20.7 mm) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There was no difference in onset age (median, 33 and 30 years old, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.391), tumor base diameter (mean, 13.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 and 12.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5 mm, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.176), or tumor height (mean, 7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2 and 7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9 mm, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.416) between the two groups. The clinical features and pregnancy outcomes of pregnant patients were shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBasic characteristics of included patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePregnant group (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-pregnant group (n\u0026thinsp;=\u0026thinsp;96)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMean Age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMax\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor Base\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.176\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTumor Height\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.416\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMetastasis case (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(15.38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18(18.75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.769\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDeath case(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(7.69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12(12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.616\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical features and pregnancy outcomes of pregnant patients after PBT (n\u0026thinsp;=\u0026thinsp;13).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge at Diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eClinical Features in Primary Survey\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTime of PBT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003ePre-Pregnancy Clinical Features\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDate of Dilivery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003ePost-Pregnancy Clinical Features\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eheight\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eheight\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eheight\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2016/10/10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2020/2/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2014/9/22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2019/9/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2015/4/20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2018/3/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eDiscovered metastasis on 2018/1/1, Dead on 2018/4/1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2019/3/11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2020/8/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eEnucleation during pregnancy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2012/3/8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2016/12/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2015/2/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2016/4/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2013/11/27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2020/9/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eEnucleation in 2014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2016/6/6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2020/5/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eEnucleation in 2017/2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2015/3/23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2016/10/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2015/5/18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2018/4/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2018/3/19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2020/10/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2013/11/6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2017/12/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eEnucleation after delivery(tumor body filled vitreous chamber)\u003c/p\u003e \u003cp\u003eDiscovered metastasis on 2018/1/31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2013/3/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2017/4/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePatient outcome\u003c/h2\u003e \u003cp\u003eThe mean follow-up time was 67.0\u0026thinsp;\u0026plusmn;\u0026thinsp;27.7 months (median:66.0 months, range:21.0 to 116.0 months). In 20 patients, metastasis had developed by the close of the study; metastatic disease was diagnosed in one woman 2 months after the birth of a child, 50 months after treatment; metastasis developed in one woman during pregnancy, and the patient died 1 month after delivery; in 18 women, with no pregnancies after diagnosis, metastases developed between 5 months and 6.8 years (median, 3.1 years) after treatment, unfortunately, twelve of which died.\u003c/p\u003e \u003cp\u003eIn the pregnant group, local recurrence of choroidal melanoma occurred in 2 patients after or during delivery, and 2 other patients developed secondary glaucoma due to radiation retinopathy. These 4 patients were treated by enucleation immediately or after delivery. Enucleation and pathology examination were conducted at local hospital or our own. All pathology result confirmed the diagnosis of uveal melanoma and revealed necrosis of most of the tumor tissue. None of the other pregnant patients who had examination before and after pregnancy (n\u0026thinsp;=\u0026thinsp;7) showed rapid tumor growth or other signs of disease progression. Local tumor recurrence, enucleation and pathological data of the control group were absent from the research.\u003c/p\u003e \u003cp\u003eSurviving women in the study were followed an average of 5.3 years after diagnosis (range, 1.8 years to 9.7 years) and the follow-up pregnancy ranged were from 7 months to 11.1 years (mean, 4.6 years). Thirteen deaths were documented and were all caused by metastatic melanoma. Metastasis and death rate of the two groups pregnant / non-pregnant were 15.38% / 18.75% and 7.69% / 12.5%, respectively. Results among the two groups (pregnant v.s. non-pregnant) showed no statistical significance of metastasis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.77) and death (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.62).\u003c/p\u003e \u003cp\u003eGiven the small sample size of patients who got pregnant, metastasis-free survival rate and survival rate may not reflect true characteristics of the two groups. We compared Metastasis-free survival months and overall survival months of both groups using Kaplan-Meier method (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Pregnant patients and matched control subjects showed no statistical difference in both aspects (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.15\u0026ndash;2.86, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.576 and HR: 0.48, 95% CI: 0.06\u0026ndash;3.66; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.464).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePregnancy\u003c/h2\u003e \u003cp\u003eAll 13 patients in the pregnant group began their pregnancy some time (median: 31 months, range: 3 to 71 months) after PBT treatment. All pregnancies were conceived naturally and were carried to term without any report of adverse events. All pregnant patients delivered healthy babies and with no report of placenta or infant metastases.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the first study to focus on the impact of pregnancy on the prognosis of UM patients treated with PBT and that based on Chinese population. Also, we were the first to discuss weather UM or PBT treatment has any effect on the physiology process of pregnancy and its outcome.\u003c/p\u003e \u003cp\u003eAbove all, our results show that the survival and metastasis rates of these patients is similar to that of women of childbearing age who had no pregnancy after treatment. This result is consistent with the absence of estrogens and progestogens in UMs(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The only two previous clinical studies(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) which focused on pregnancy occurred after the treatment of UM also supports our findings. Similar to our report, both studies treated most their patients with conservative treatment primarily such as proton beam irradiation or brachytherapy. Therefore, These findings of similar prognosis among patients who had or didn\u0026rsquo;t have children after PBT may also be the result of the cessation of mitotic activity and tumor cell necrosis in most patients after local radiotherapy(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, there have been occasional cases of significantly increased UM during pregnancy over the past few decades(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Lee et.al reported a 31-year-old woman with a 29-week pregnancy was diagnosed with uveal melanoma(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). She refused any treatment for the remaining three months of her pregnancy and the tumor increased in size from 8\u0026times;5 mm\u003csup\u003e2\u003c/sup\u003e to 13\u0026times;12 mm\u003csup\u003e2\u003c/sup\u003e. Recently, Yue et.al. reported the first Chinese case of accelerate growth of UM during pregnancy and the tumor showed a rapid growth rate and extended to the orbit with muscle invasion. Similar to the previous case, the patient did not receive any treatment before the end of pregnancy, also there was no detailed medical report but only the subjective feelings of the patient prior to pregnancy. Combining previous retrospective case-control studies and reports of these two cases, we suggest that UM patients treated with local radiation therapy is probably unaffected by hormonal and ocular physiological changes during pregnancy.\u003c/p\u003e \u003cp\u003eAlso, similar to some previous studies, we demonstrated that UM had no significant impact on maternal fertility for there had been hundreds of cases reported of UM discovered during pregnant and UM patients getting pregnant(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Among all these reports, including our own, and the vast number of cases that they have reported, we found only one case report of placental metastasis attributed to choroidal melanoma(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), and none fetal metastasis. Therefore, we can draw a preliminary conclusion that it is extremely unlikely for choroidal melanoma to metastasize to fetus. Additionally, we also proved that the plaque brachytherapy with localized radiation also has neither significant effect on maternal fertility, nor teratogenic effect on the fetus.\u003c/p\u003e \u003cp\u003eSome limitations of this study should be also noted. First of all, like previous studies, the number of pregnant cases in this study was limited. UM is a rare disease with most patients presenting between the ages of 50 years and 70 years(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is estimated to have an incidence rate of four to eight per million, with a reported higher rate among men(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Therefore, few women of childbearing age have a history of uveal melanoma. Additionally, although survivors of non-reproductive organ cancer had similar birth rates as the background population(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), in clinical practice, many patients gave up the idea of having children upon diagnosis of malignant tumor. These factors have limited the number of cases in studies of pregnancy in UM patients after treatment. Secondly, according to follow-up, gross examination of the placenta did not show any evidence of metastatic disease, and since none of the pregnant patients gave birth in our hospital, none of the specimen underwent microscopic examination. We believe that pathological examination of the placenta should be performed as described by previous study(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) to accurately exclude placental metastases.\u003c/p\u003e \u003cp\u003eIn the past 20 years, few articles have focused on this issue, and we hope to attract researchers' attention to women of reproductive age with malignant tumors. Further clinical and basic studies are needed to draw more definitive conclusions.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eDespite these controversies and limitations, the results of this study are a great piece of good news for UM patients with fertility needs, and also provide valuable reference for clinicians to provide fertility guidance to UM patients. We demonstrated that the prognosis of women with uveal melanoma who underwent PBT is not influenced by pregnancy. Also, plaque brachytherapy had no significant effect on maternal fertility, and did not show teratogenic effect on the fetus so far. Therefore, if a patient conceives after the diagnosis of UM and underwent PBT, pregnancy termination is not necessary, but a close ophthalmological follow-up until delivery and a regular ophthalmologic examination of the baby is strongly advised.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the ethical committee of Beijing Tongren Hospital of Capital Medical University. Research adhered to the tenets of the Declaration of Helsinki. All adult subjects (Age\u0026ge;18 years old) involved in the clinical data used in this study signed written informed consent. The informed consent of subjects who were less than 18 years old was signed by their guardian.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearch data of this study are not publicly available\u0026nbsp;on legal grounds. Data can be made available from the corresponding author on a reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by National Natural Science Foundation of China (82141128); The Capital Health Research and Development of Special (2020-1-2052); Science \u0026amp; Technology Project of Beijing Municipal Science \u0026amp; Technology Commission (Z201100005520045, Z181100001818003)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design of the research: HTW, YML and WBW; Acquisition and interpretation of the data: HTW, YML, WBW and DL, RHZ, WDZ, HYL; Statistical analysis and writing of the manuscript: HTW, YML, DL, RHZ and HYL; Critical revision of the manuscript: HTW and WBW.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJager MJ, Shields CL, Cebulla CM, Abdel-Rahman MH, Grossniklaus HE, Stern MH, et al. Uveal melanoma. Nat Rev Dis Primers. 2020;6(1):24.\u003c/li\u003e\n\u003cli\u003eSingh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118(9):1881-5.\u003c/li\u003e\n\u003cli\u003eShields CL, Shields JA, Cater J, z KGn, Miyamoto C, Micaily B, et al. Plaque Radiotherapy for Uveal Melanoma: Long-term Visual Outcome in 1106 Consecutive Patients. Arch Ophthalmol. 2000(118):1219-28.\u003c/li\u003e\n\u003cli\u003eDiener-West M, Earle JD, Fine SL. The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma, III: Initial Mortality Findings. AMA archives of ophthalmology. 2001(119):969-82.\u003c/li\u003e\n\u003cli\u003eJampol LM, Moy CS, Murray TG, Reynolds SM, Albert DM, Schachat AP, et al. The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma: IV. Local Treatment Failure and Enucleation in the First 5 Years after Brachytherapy. COMS Report No. 19. Ophthalmology. 2020;127(4S):S148-S57.\u003c/li\u003e\n\u003cli\u003eSingh N, Bergman L, Seregard S, Singh AD. Uveal Melanoma: Epidemiologic Aspect. Springer Berlin Heidelberg. 2014.\u003c/li\u003e\n\u003cli\u003eKaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. Eye (Lond). 2017;31(2):241-57.\u003c/li\u003e\n\u003cli\u003eHartman M, Liu J, Czene K, Miao H, Chia KS, Salim A, et al. Birth rates among female cancer survivors: a population-based cohort study in Sweden. Cancer. 2013;119(10):1892-9.\u003c/li\u003e\n\u003cli\u003eNaderan M. Ocular changes during pregnancy. J Curr Ophthalmol. 2018;30(3):202-10.\u003c/li\u003e\n\u003cli\u003eHartge P, Tucker MA, Shields JA, Augsburger J, Hoover RN, Joseph F. Fraumeni J. Case-Control Study of Female Hormones and Eye Melanoma. cancer resaearch. 1989(49):4622-5.\u003c/li\u003e\n\u003cli\u003eZinkhan M, Stang A, Jockel KH, Marr A, Bornfeld N, Schmidt-Pokrzywniak A. Having children, social characteristics, smoking and the risk of uveal melanoma: a case-control study. Ophthalmic Epidemiol. 2013;20(6):360-8.\u003c/li\u003e\n\u003cli\u003eHolly EA, Aston DA, Ahn DK, Kristiansen JJ, Char DH. Uveal Melanoma, Hormonal and Reproductive Factors in Women. cancer resaearch. 1991(51):1370-2.\u003c/li\u003e\n\u003cli\u003eEgan KM, Walsh SM, Seddon JM, Gragoudas ES. An Evaluation of the Influence of Reproductive Factors on the Risk of Metastases from Uveal Melanoma. Ophthalmology. 1993(100):1160-6.\u003c/li\u003e\n\u003cli\u003eLemaitre S, Levy-Gabriel C, Desjardins L, Plancher C, Asselain B, Vincent-Salomon A, et al. Choroidal melanoma and pregnancy. Acta Ophthalmol. 2016;94(7):e652-e60.\u003c/li\u003e\n\u003cli\u003eEgan KM, Quinn JL, Gragoudas ES. Childbearing History Associated With Improved Survival in Choroidal Melanoma. Arch Ophthalmol. 1999(117):939-42.\u003c/li\u003e\n\u003cli\u003eSeddon JM, Maclaughlin DT, Albert DM, Gragoudas ES, III MF. Uveal melanoma presenting during pregnancy and the investigation of oestrogen receptors in melanomas. British Journal of Ophthalmology. 1982(66):695-704.\u003c/li\u003e\n\u003cli\u003eLee CS, Yang WI, Shin KJ, Lee SC. Rapid growth of choroidal melanoma during pregnancy. Acta Ophthalmol. 2011;89(3):e290-1.\u003c/li\u003e\n\u003cli\u003eYue H, Qian J, Ren H, Zhang R, Gan L, Bi YW. Accelerated growth of uveal melanoma related to pregnancy: a case report and literature review. Int J Ophthalmol. 2021;14(2):326-9.\u003c/li\u003e\n\u003cli\u003eShields CL, Shields JA, Karlsson U, Menduke H, Brady LW. Enucleation after Plague Radiotherapy for Posterior Uveal Melanoma. Ophthalmology. 1990;97(12):1665-70.\u003c/li\u003e\n\u003cli\u003eShields CL, Shields JA, Jr. RCE, Potter PD, Menduke H. Uveal Melanoma and Pregnancy: A Report of 16 Cases. Ophthalmology. 1991;98(98):1667-73.\u003c/li\u003e\n\u003cli\u003eMiller E, Barnea Y, Gur E, Leshem D, Karin E, Weiss J, et al. Malignant melanoma and pregnancy: second thoughts. J Plast Reconstr Aesthet Surg. 2010;63(7):1163-8.\u003c/li\u003e\n\u003cli\u003eSchmidt-Pokrzywniak A, Kalbitz S, Kuss O, Jöckel K-H, Bornfeld N, Stang A. Assessment of the effect of iris colour and having children on 5-year risk of death after diagnosis of uveal melanoma: a follow-up study. BMC Ophthalmology. 2014;14:42.\u003c/li\u003e\n\u003cli\u003eMarsh RdW, Chu N-M. Placental metastasis from primary ocular melanoma: A case report. Am J Obstet Gynecol. 1996(174):1654-5.\u003c/li\u003e\n\u003cli\u003ePark SJ, Oh CM, Kim BW, Woo SJ, Cho H, Park KH. Nationwide Incidence of Ocular Melanoma in South Korea by Using the National Cancer Registry Database (1999-2011). Invest Ophthalmol Vis Sci. 2015;56(8):4719-24.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pregnancy, Uveal melanoma, Plaque brachytherapy","lastPublishedDoi":"10.21203/rs.3.rs-3094982/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3094982/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo examine whether pregnancy affects the prognosis of uveal melanoma (UM) patients undergoing plaque brachytherapy (PBT) and if PBT has any effect on the outcome of such pregnancy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a single-center retrospective study at the Beijing Tongren Hospital on the population of women with childbearing age who were diagnosed with uveal melanoma and underwent iodine-125 plaque brachytherapy. The outcome of each pregnancy and the status of the fetus was followed-up. Survival analysis were performed using Kaplan-Meier method, with the metastasis and death as endpoints.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e13 patients with 13 full-term pregnancies and 96 non-pregnant women with matched age and tumor size were included. In pregnant group, two patients developed metastasis, one of which died shortly after delivery; local recurrence of UM occurred in 2 patients after or during delivery, and 2 other patients developed secondary glaucoma due to radiation retinopathy. None of the other pregnant patients reported any signs of disease progression. In the control group, 18 metastasis cases including 12 deaths were documented. Pregnant patients and matched control subjects showed no statistical difference in both Metastasis-free survival (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.15\u0026ndash;2.86; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.576) and overall survival (HR: 0.48, 95% CI: 0.06\u0026ndash;3.66; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.464). All pregnant patients carried the pregnancy to term and delivered healthy babies with no report of placental or infant metastases to date.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePregnancy exerted no adverse effects on the prognosis of UM patients who receive PBT. While PBT had no significant effect on maternal fertility, and did not show teratogenic effect on the fetus so far, long-term effects require further follow-up studies.\u003c/p\u003e","manuscriptTitle":"Pregnancy and Plaque Brachytherapy Treatment of Uveal Melanoma：A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-07-07 14:06:05","doi":"10.21203/rs.3.rs-3094982/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-01-27T21:00:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-01-27T19:53:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-08-18T09:32:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"c45a68b6-4ad9-4f2a-b52f-a45f2953e9e6","date":"2023-08-10T06:40:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-07-10T15:45:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-07-10T15:43:43+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-07-04T04:49:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-07-04T04:47:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2023-06-22T07:09:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"368c7ce4-0588-4f3f-93bd-1965954001cd","owner":[],"postedDate":"July 7th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-30T16:01:33+00:00","versionOfRecord":{"articleIdentity":"rs-3094982","link":"https://doi.org/10.1186/s12886-024-03681-6","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2024-09-27 15:57:22","publishedOnDateReadable":"September 27th, 2024"},"versionCreatedAt":"2023-07-07 14:06:05","video":"","vorDoi":"10.1186/s12886-024-03681-6","vorDoiUrl":"https://doi.org/10.1186/s12886-024-03681-6","workflowStages":[]},"version":"v1","identity":"rs-3094982","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3094982","identity":"rs-3094982","version":["v1"]},"buildId":"DfRiq_wiF3Ryq-tyrab2w","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}