Abstract
PURPOSE: To quantitate long-term risk of local treatment failure after proton irradiation of choroidal/ciliary body melanomas and to evaluate risk of metastasis-related deaths after local failure. METHODS: We followed prospectively 1,922 patients treated at the Harvard Cyclotron between January 1975 and December 1996 for local recurrences of their tumors. Mortality surveillance was completed through June 1999. For analysis, patient follow-up continued until tumor regrowth was detected or, in patients without recurrence, until the date of the last dilated examination prior to April 1998. Actuarial methods were used to calculate rates of recurrence and metastatic deaths. Cox regression models were constructed to evaluate risk factors for these outcomes. RESULTS: Median ocular follow-up after irradiation was 5.2 years. Local recurrence was documented in 45 patients by ultrasound and/or sequential fundus photographs; in 17 more patients, the eye was enucleated due to suspected but unconfirmed tumor growth. Recurrences were documented between 2 months and 11.3 years after irradiation. The 5- and 10-year rates of regrowth, including suspected cases, were 3.2% (95% confidence interval [CI], 2.5%-4.2%), and 4.3% (95% CI, 3.3%-5.6%). Among the 45 documented recurrences, about one half (21) occurred at the margin, presumably due to treatment planning errors. The remaining cases represented extrascleral extensions (nine cases), ring melanomas (six cases), or uncontrolled tumor (nine cases). Recurrence of the tumor was independently related to risk of tumor-related death. CONCLUSION: These data, based on relatively long-term follow-up, demonstrate that excellent local control is maintained after proton therapy and that patients with recurrences experience poorer survival.
Full Text
The Full Text of this article is available as a PDF (39.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aalto Y., Eriksson L., Seregard S., Larsson O., Knuutila S. Concomitant loss of chromosome 3 and whole arm losses and gains of chromosome 1, 6, or 8 in metastasizing primary uveal melanoma. Invest Ophthalmol Vis Sci. 2001 Feb;42(2):313–317. [PubMed] [Google Scholar]
- Adams K. S., Abramson D. H., Ellsworth R. M., Haik B. G., Bedford M., Packer S., Seddon J., Albert D., Polivogianis L. Cobalt plaque versus enucleation for uveal melanoma: comparison of survival rates. Br J Ophthalmol. 1988 Jul;72(7):494–497. doi: 10.1136/bjo.72.7.494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Augsburger J. J., Corrêa Z. M., Freire J., Brady L. W. Long-term survival in choroidal and ciliary body melanoma after enucleation versus plaque radiation therapy. Ophthalmology. 1998 Sep;105(9):1670–1678. doi: 10.1016/S0161-6420(98)99037-6. [DOI] [PubMed] [Google Scholar]
- Augsburger J. J., Goel S. D. Visual function following enucleation or episcleral plaque radiotherapy for posterior uveal melanoma. Arch Ophthalmol. 1994 Jun;112(6):786–789. doi: 10.1001/archopht.1994.01090180084039. [DOI] [PubMed] [Google Scholar]
- Castro J. R., Char D. H., Petti P. L., Daftari I. K., Quivey J. M., Singh R. P., Blakely E. A., Phillips T. L. 15 years experience with helium ion radiotherapy for uveal melanoma. Int J Radiat Oncol Biol Phys. 1997 Dec 1;39(5):989–996. doi: 10.1016/s0360-3016(97)00494-x. [DOI] [PubMed] [Google Scholar]
- Char D. H., Kroll S., Quivey J. M., Castro J. Long term visual outcome of radiated uveal melanomas in eyes eligible for randomisation to enucleation versus brachytherapy. Br J Ophthalmol. 1996 Feb;80(2):117–124. doi: 10.1136/bjo.80.2.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Char D. H., Quivey J. M., Castro J. R., Kroll S., Phillips T. Helium ions versus iodine 125 brachytherapy in the management of uveal melanoma. A prospective, randomized, dynamically balanced trial. Ophthalmology. 1993 Oct;100(10):1547–1554. doi: 10.1016/s0161-6420(93)31446-6. [DOI] [PubMed] [Google Scholar]
- Diener-West M., Earle J. D., Fine S. L., Hawkins B. S., Moy C. S., Reynolds S. M., Schachat A. P., Straatsma B. R., Collaborative Ocular Melanoma Study Group The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch Ophthalmol. 2001 Jul;119(7):969–982. doi: 10.1001/archopht.119.7.969. [DOI] [PubMed] [Google Scholar]
- Egan K. M., Ryan L. M., Gragoudas E. S. Survival implications of enucleation after definitive radiotherapy for choroidal melanoma: an example of regression on time-dependent covariates. Arch Ophthalmol. 1998 Mar;116(3):366–370. doi: 10.1001/archopht.116.3.366. [DOI] [PubMed] [Google Scholar]
- Egan K. M., Ryan L. M., Gragoudas E. S. Survival implications of enucleation after definitive radiotherapy for choroidal melanoma: an example of regression on time-dependent covariates. Arch Ophthalmol. 1998 Mar;116(3):366–370. doi: 10.1001/archopht.116.3.366. [DOI] [PubMed] [Google Scholar]
- Egger E., Schalenbourg A., Zografos L., Bercher L., Boehringer T., Chamot L., Goitein G. Maximizing local tumor control and survival after proton beam radiotherapy of uveal melanoma. Int J Radiat Oncol Biol Phys. 2001 Sep 1;51(1):138–147. doi: 10.1016/s0360-3016(01)01560-7. [DOI] [PubMed] [Google Scholar]
- Folberg R., Mehaffey M., Gardner L. M., Meyer M., Rummelt V., Pe'er J. The microcirculation of choroidal and ciliary body melanomas. Eye (Lond) 1997;11(Pt 2):227–238. doi: 10.1038/eye.1997.57. [DOI] [PubMed] [Google Scholar]
- Folberg R., Rummelt V., Parys-Van Ginderdeuren R., Hwang T., Woolson R. F., Pe'er J., Gruman L. M. The prognostic value of tumor blood vessel morphology in primary uveal melanoma. Ophthalmology. 1993 Sep;100(9):1389–1398. doi: 10.1016/s0161-6420(93)31470-3. [DOI] [PubMed] [Google Scholar]
- Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
- Gradoudas E. S., Goitein M., Koehler A., Constable I. J., Wagner M. S., Verhey L., Tepper J., Suit H. D., Brockhurst R. J., Schneider R. J. Proton irradiation of choroidal melanomas. Preliminary results. Arch Ophthalmol. 1978 Sep;96(9):1583–1591. doi: 10.1001/archopht.1978.03910060217006. [DOI] [PubMed] [Google Scholar]
- Gragoudas E. S. 1996 Jules Gonin Lecture of the Retina Research Foundation. Long-term results after proton irradiation of uveal melanomas. Graefes Arch Clin Exp Ophthalmol. 1997 May;235(5):265–267. doi: 10.1007/BF01739634. [DOI] [PubMed] [Google Scholar]
- Gragoudas E. S., Egan K. M., Seddon J. M., Walsh S. M., Munzenrider J. E. Intraocular recurrence of uveal melanoma after proton beam irradiation. Ophthalmology. 1992 May;99(5):760–766. doi: 10.1016/s0161-6420(92)31900-1. [DOI] [PubMed] [Google Scholar]
- Gragoudas E. S., Goitein M., Verhey L., Munzenreider J., Urie M., Suit H., Koehler A. Proton beam irradiation of uveal melanomas. Results of 5 1/2-year study. Arch Ophthalmol. 1982 Jun;100(6):928–934. doi: 10.1001/archopht.1982.01030030936007. [DOI] [PubMed] [Google Scholar]
- Gragoudas E. S., Lane A. M., Regan S., Li W., Judge H. E., Munzenrider J. E., Seddon J. M., Egan K. M. A randomized controlled trial of varying radiation doses in the treatment of choroidal melanoma. Arch Ophthalmol. 2000 Jun;118(6):773–778. doi: 10.1001/archopht.118.6.773. [DOI] [PubMed] [Google Scholar]
- Gragoudas E. S., Seddon J. M., Egan K. M., Glynn R. J., Goitein M., Munzenrider J., Verhey L., Urie M., Koehler A. Metastasis from uveal melanoma after proton beam irradiation. Ophthalmology. 1988 Jul;95(7):992–999. doi: 10.1016/s0161-6420(88)33091-5. [DOI] [PubMed] [Google Scholar]
- Gragoudas E. S., Seddon J. M., Egan K. M., Polivogianis L., Hsieh C. C., Goitein M., Verhey L., Munzenrider J., Austin-Seymour M., Urie M. Prognostic factors for metastasis following proton beam irradiation of uveal melanomas. Ophthalmology. 1986 May;93(5):675–680. doi: 10.1016/s0161-6420(86)33699-6. [DOI] [PubMed] [Google Scholar]
- Gragoudas E. S., Seddon J., Goitein M., Verhey L., Munzenrider J., Urie M., Suit H. D., Blitzer P., Koehler A. Current results of proton beam irradiation of uveal melanomas. Ophthalmology. 1985 Feb;92(2):284–291. doi: 10.1016/s0161-6420(85)34058-7. [DOI] [PubMed] [Google Scholar]
- Harbour J. W., Char D. H., Kroll S., Quivey J. M., Castro J. Metastatic risk for distinct patterns of postirradiation local recurrence of posterior uveal melanoma. Ophthalmology. 1997 Nov;104(11):1785–1793. doi: 10.1016/s0161-6420(97)30025-6. [DOI] [PubMed] [Google Scholar]
- Hill J. C., Sealy R., Shackleton D., Stannard C., Korrubel J., Hering E., Loxton C. Improved iodine-125 plaque design in the treatment of choroidal malignant melanoma. Br J Ophthalmol. 1992 Feb;76(2):91–94. doi: 10.1136/bjo.76.2.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karlsson U. L., Augsburger J. J., Shields J. A., Markoe A. M., Brady L. W., Woodleigh R. Recurrence of posterior uveal melanoma after 60Co episcleral plaque therapy. Ophthalmology. 1989 Mar;96(3):382–388. doi: 10.1016/s0161-6420(89)32882-x. [DOI] [PubMed] [Google Scholar]
- Kroll S., Char D. H., Quivey J., Castro J. A comparison of cause-specific melanoma mortality and all-cause mortality in survival analyses after radiation treatment for uveal melanoma. Ophthalmology. 1998 Nov;105(11):2035–2045. doi: 10.1016/S0161-6420(98)91121-6. [DOI] [PubMed] [Google Scholar]
- Li W., Gragoudas E. S., Egan K. M. Metastatic melanoma death rates by anatomic site after proton beam irradiation for uveal melanoma. Arch Ophthalmol. 2000 Aug;118(8):1066–1070. doi: 10.1001/archopht.118.8.1066. [DOI] [PubMed] [Google Scholar]
- Manschot W. A., Lee W. R., van Strik R. Uveal melanoma: updated considerations on current management modalities. Int Ophthalmol. 1995;19(4):203–209. doi: 10.1007/BF00132688. [DOI] [PubMed] [Google Scholar]
- Melia B. M., Abramson D. H., Albert D. M., Boldt H. C., Earle J. D., Hanson W. F., Montague P., Moy C. S., Schachat A. P., Simpson E. R. Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology. 2001 Feb;108(2):348–366. doi: 10.1016/s0161-6420(00)00526-1. [DOI] [PubMed] [Google Scholar]
- Munzenrider J. E. Uveal melanomas. Conservation treatment. Hematol Oncol Clin North Am. 2001 Apr;15(2):389–402. doi: 10.1016/s0889-8588(05)70219-7. [DOI] [PubMed] [Google Scholar]
- Munzenrider J. E., Verhey L. J., Gragoudas E. S., Seddon J. M., Urie M., Gentry R., Birnbaum S., Ruotolo D. M., Crowell C., McManus P. Conservative treatment of uveal melanoma: local recurrence after proton beam therapy. Int J Radiat Oncol Biol Phys. 1989 Sep;17(3):493–498. doi: 10.1016/0360-3016(89)90099-0. [DOI] [PubMed] [Google Scholar]
- O'Reilly M. S., Holmgren L., Shing Y., Chen C., Rosenthal R. A., Moses M., Lane W. S., Cao Y., Sage E. H., Folkman J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994 Oct 21;79(2):315–328. doi: 10.1016/0092-8674(94)90200-3. [DOI] [PubMed] [Google Scholar]
- Quivey J. M., Augsburger J., Snelling L., Brady L. W. 125I plaque therapy for uveal melanoma. Analysis of the impact of time and dose factors on local control. Cancer. 1996 Jun 1;77(11):2356–2362. doi: 10.1002/(SICI)1097-0142(19960601)77:11<2356::AID-CNCR26>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
- Rummelt V., Folberg R., Woolson R. F., Hwang T., Pe'er J. Relation between the microcirculation architecture and the aggressive behavior of ciliary body melanomas. Ophthalmology. 1995 May;102(5):844–851. doi: 10.1016/s0161-6420(95)30947-5. [DOI] [PubMed] [Google Scholar]
- Scotto J., Fraumeni J. F., Jr, Lee J. A. Melanomas of the eye and other noncutaneous sites: epidemiologic aspects. J Natl Cancer Inst. 1976 Mar;56(3):489–491. doi: 10.1093/jnci/56.3.489. [DOI] [PubMed] [Google Scholar]
- Seddon J. M., Gragoudas E. S., Egan K. M., Glynn R. J., Howard S., Fante R. G., Albert D. M. Relative survival rates after alternative therapies for uveal melanoma. Ophthalmology. 1990 Jun;97(6):769–777. doi: 10.1016/s0161-6420(90)32512-5. [DOI] [PubMed] [Google Scholar]
- Shields C. L., Shields J. A., Cater J., Gündüz K., Miyamoto C., Micaily B., Brady L. W. Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients. Arch Ophthalmol. 2000 Sep;118(9):1219–1228. doi: 10.1001/archopht.118.9.1219. [DOI] [PubMed] [Google Scholar]
- Sisley K., Cottam D. W., Rennie I. G., Parsons M. A., Potter A. M., Potter C. W., Rees R. C. Non-random abnormalities of chromosomes 3, 6, and 8 associated with posterior uveal melanoma. Genes Chromosomes Cancer. 1992 Oct;5(3):197–200. doi: 10.1002/gcc.2870050304. [DOI] [PubMed] [Google Scholar]
- Sisley K., Rennie I. G., Parsons M. A., Jacques R., Hammond D. W., Bell S. M., Potter A. M., Rees R. C. Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes Chromosomes Cancer. 1997 May;19(1):22–28. doi: 10.1002/(sici)1098-2264(199705)19:1<22::aid-gcc4>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
- Suit H. D. Local control and patient survival. Int J Radiat Oncol Biol Phys. 1992;23(3):653–660. doi: 10.1016/0360-3016(92)90025-d. [DOI] [PubMed] [Google Scholar]
- Suit H., Urie M. Proton beams in radiation therapy. J Natl Cancer Inst. 1992 Feb 5;84(3):155–164. doi: 10.1093/jnci/84.3.155. [DOI] [PubMed] [Google Scholar]
- Vrabec T. R., Augsburger J. J., Gamel J. W., Brady L. W., Hernandez C., Woodleigh R. Impact of local tumor relapse on patient survival after cobalt 60 plaque radiotherapy. Ophthalmology. 1991 Jun;98(6):984–988. doi: 10.1016/s0161-6420(91)32193-6. [DOI] [PubMed] [Google Scholar]
- Withers H. R. Biological basis of radiation therapy for cancer. Lancet. 1992 Jan 18;339(8786):156–159. doi: 10.1016/0140-6736(92)90218-r. [DOI] [PubMed] [Google Scholar]