Intraocular involvement is associated with a high risk of disease relapse in primary central nervous system lymphoma

Zhuang,Lin; Lai,Jie; Chen,Kun; Ding,Tianling; Yuan,Yan; Ma,Yan; Kang,Hui; Lin,Zhiguang; Fan,Ni; Ma,Jingjing; Zeng,Qingchao; Xu,Xiaoping; Wang,Qingping; Chen,Bobin

doi:10.3892/or.2018.6781

Intraocular involvement is associated with a high risk of disease relapse in primary central nervous system lymphoma

Authors:
- Lin Zhuang
- Jie Lai
- Kun Chen
- Tianling Ding
- Yan Yuan
- Yan Ma
- Hui Kang
- Zhiguang Lin
- Ni Fan
- Jingjing Ma
- Qingchao Zeng
- Xiaoping Xu
- Qingping Wang
- Bobin Chen
View Affiliations

Affiliations: Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Laboratory Medicine, Huashan Hospital North, Fudan University, Shanghai 200040, P.R. China, Department of Hematology, Huashan Hospital North, Fudan University, Shanghai 200040, P.R. China
Published online on: October 11, 2018 https://doi.org/10.3892/or.2018.6781
Pages: 397-404

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to prospectively evaluate the recurrence and survival outcome of primary central nervous system lymphoma (PCNSL) with intraocular involvement. For this purpose, a prospective cohort of 103 pathologically confirmed patients with PCNSL was enrolled in this study. Ophthalmologic examinations were performed both at diagnosis and during follow‑up. The patients with PCNSL with suspected intraocular involvement underwent vitrectomy for confirmation. Patients who presented with intraocular involvement either at diagnosis or during disease progression were allocated to the intraocular lymphoma (IOL) group. All patients with PCNSL received systemic methotrexate (MTX)‑based chemotherapy with or without radiotherapy. MTX intravitreal injection combined with systemic MTX‑based chemotherapy was recommended once ocular lesions were confirmed. Recurrent intraocular and central nervous system (CNS) events, progression‑free survival (PFS) and overall survival (OS) outcomes were analyzed. The findings of this study revealed that 21 patients with PCNSL exhibited intraocular involvement. One patient with IOL presented with isolated ocular lymphoma at the initial diagnosis, and the others presented with ocular involvement along with CNS invasion during the course of the disease. A total of 14 patients received systemic MTX‑based chemotherapy prior to the diagnosis of IOL. The recurrence rates in patients with or without intraocular involvement were 71.4 and 46.3%, respectively (P=0.04) and the relapse sites in the patients with IOL included the brain (3 patients), eyes (6 patients), and both brain and eyes (6 cases). The median PFS was 13 months in the IOL group and 19 months in the patients without intraocular involvement (non‑IOL) (P=0.019). The median OS was 51 months vs. 56 months, respectively (P=0.312). There was no signiﬁcant difference in the 2‑year PFS and OS rates between the 2 groups (23.8% vs. 23.2%, P=0.951; and 61.9% vs. 41.4%, P=0.093, respectively). On the whole, the findings of this study suggest that patients with IOL have a high risk of relapse and a poor PFS compared to patients without IOL, but a similar OS.

View Figures

View References

1	Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, Smith JR, Korfel A, Soussain C, DeAngelis LM, et al: Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol. 23:pp. 5034–5043. 2005, View Article : Google Scholar : PubMed/NCBI
2	Chan CC, Rubenstein JL, Coupland SE, Davis JL, Harbour JW, Johnston PB, Cassoux N, Touitou V, Smith JR, Batchelor TT, et al: Primary vitreoretinal lymphoma: A report from an international primary central nervous system lymphoma collaborative group symposium. Oncologist. 16:1589–1599. 2011. View Article : Google Scholar : PubMed/NCBI
3	Peterson K, Gordon KB, Heinemann MH and DeAngelis LM: The clinical spectrum of ocular lymphoma. Cancer-Am Cancer Soc. 72:843–849. 1993.
4	Nussenblatt RB, Chan CC, Wilson WH, Hochman J and Gottesman M: International Central Nervous System and Ocular Lymphoma Workshop: Recommendations for the future. Ocul Immunol Inflamm. 14:139–144. 2006. View Article : Google Scholar : PubMed/NCBI
5	Sung CO, Kim SC, Karnan S, Karube K, Shin HJ, Nam DH, Suh YL, Kim SH, Kim JY, Kim SJ, et al: Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma. Blood. 117:1291–1300. 2011. View Article : Google Scholar : PubMed/NCBI
6	Kim MM, Dabaja BS, Medeiros J, Kim S, Allen P, Chevez-Barrios P, Gombos DS and Fowler N: Survival outcomes of primary intraocular lymphoma: A single-institution experience. Am J Clin Oncol. 39:109–113. 2016. View Article : Google Scholar : PubMed/NCBI
7	Wang L, Sato-Otsubo A, Sugita S, Takase H, Mochizuki M, Usui Y, Goto H, Koyama T, Akiyama H, Miura O, et al: High-resolution genomic copy number profiling of primary intraocular lymphoma by single nucleotide polymorphism microarrays. Cancer Sci. 105:592–599. 2014. View Article : Google Scholar : PubMed/NCBI
8	Mulay K, Narula R and Honavar SG: Primary vitreoretinal lymphoma. Indian J Ophthalmol. 63:180–186. 2015. View Article : Google Scholar : PubMed/NCBI
9	Witmer MT: Primary vitreoretinal lymphoma: Management of isolated ocular disease. Cancer Control. 23:110–116. 2016. View Article : Google Scholar : PubMed/NCBI
10	Stubiger N, Kakkassery V, Gundlach E, Winterhalter S and Pleyer U: Diagnostics and treatment of primary vitreoretinal lymphoma. Ophthalmologe. 112:223–230. 2015.(In German). View Article : Google Scholar : PubMed/NCBI
11	Rajagopal R and Harbour JW: Diagnostic testing and treatment choices in primary vitreoretinal lymphoma. Retina. 31:435–440. 2011. View Article : Google Scholar : PubMed/NCBI
12	Cho BJ, Kim DY, Park UC, Lee JY, Yoon YH and Yu HG: Clinical features and treatment outcomes of vitreoretinal lymphoma according to its association with CNS lymphoma. Ocul Immunol Inflamm. 26:365–371. 2018. View Article : Google Scholar : PubMed/NCBI
13	Ahle G, Touitou V, Cassoux N, Bouyon M, Humbrecht C, Oesterlé H, Baraniskin A, Soussain C, Nguyen-Them L, Gaultier C, et al: Optic nerve infiltration in primary central nervous system lymphoma. Jama Neurol. 74:1368–1373. 2017. View Article : Google Scholar : PubMed/NCBI
14	Grimm SA, McCannel CA, Omuro AM, Ferreri AJ, Blay JY, Neuwelt EA, Siegal T, Batchelor T, Jahnke K, Shenkier TN, et al: Primary CNS lymphoma with intraocular involvement: International PCNSL Collaborative Group Report. Neurology. 71:pp. 1355–1360. 2008, View Article : Google Scholar : PubMed/NCBI
15	Kreher S, Strehlow F, Martus P, Roth P, Hertenstein B, Röth A, Birnbaum T, Griesinger F, Rauch M, Kanz L, et al: Prognostic impact of intraocular involvement in primary CNS lymphoma: Experience from the G-PCNSL-SG1 trial. Ann Hematol. 94:409–414. 2015. View Article : Google Scholar : PubMed/NCBI
16	Jahnke K, Korfel A, Komm J, Bechrakis NE, Stein H, Thiel E and Coupland SE: Intraocular lymphoma 2000–2005: Results of a retrospective multicentre trial. Graefes Arch Clin Exp Ophthalmol. 244:663–669. 2006. View Article : Google Scholar : PubMed/NCBI
17	Kaburaki T, Taoka K, Matsuda J, Yamashita H, Matsuda I, Tsuji H, Tanaka R, Nakazaki K, Nakamura F, Kamiya K, et al: Combined intravitreal methotrexate and immunochemotherapy followed by reduced-dose whole-brain radiotherapy for newly diagnosed B-cell primary intraocular lymphoma. Br J Haematol. 179:246–255. 2017. View Article : Google Scholar : PubMed/NCBI
18	Langner-Lemercier S, Houillier C, Soussain C, Ghesquières H, Chinot O, Taillandier L, Soubeyran P, Lamy T, Morschhauser F, Benouaich-Amiel A, et al: Primary CNS lymphoma at first relapse/progression: Characteristics, management, and outcome of 256 patients from the French LOC network. Neuro Oncol. 18:1297–1303. 2016. View Article : Google Scholar : PubMed/NCBI
19	Nayak L, Hedvat C, Rosenblum MK, Abrey LE and DeAngelis LM: Late relapse in primary central nervous system lymphoma: Clonal persistence. Neuro Oncol. 13:525–529. 2011. View Article : Google Scholar : PubMed/NCBI
20	Kim JE, Yoon DH, Kim S, Lee DH, Kim JH, Yoon YH, Chi HS, Lee SW, Park CS, Huh J and Suh C: Relapse pattern and prognostic factors for patients with primary central nervous system lymphoma. Korean J Hematol. 47:60–66. 2012. View Article : Google Scholar : PubMed/NCBI
21	Ferreri AJ, Blay JY, Reni M, Pasini F, Gubkin A, Tirelli U, Calderoni A, Zucca E, Cortelazzo S, Chassagne C, et al: Relevance of intraocular involvement in the management of primary central nervous system lymphomas. Ann Oncol. 13:531–538. 2002. View Article : Google Scholar : PubMed/NCBI
22	Fend F, Ferreri AJ and Coupland SE: How we diagnose and treat vitreoretinal lymphoma. Br J Haematol. 173:680–692. 2016. View Article : Google Scholar : PubMed/NCBI
23	Coupland SE, Bechrakis NE, Anastassiou G, Foerster AM, Heiligenhaus A, Pleyer U, Hummel M and Stein H: Evaluation of vitrectomy specimens and chorioretinal biopsies in the diagnosis of primary intraocular lymphoma in patients with Masquerade syndrome. Graefes Arch Clin Exp Ophthalmol. 241:860–870. 2003. View Article : Google Scholar : PubMed/NCBI
24	Sugita S, Takase H, Sugamoto Y, Arai A, Miura O and Mochizuki M: Diagnosis of intraocular lymphoma by polymerase chain reaction analysis and cytokine profiling of the vitreous fluid. JPN J Ophthalmol. 53:209–214. 2009. View Article : Google Scholar : PubMed/NCBI
25	Chan CC, Whitcup SM, Solomon D and Nussenblatt RB: Interleukin-10 in the vitreous of patients with primary intraocular lymphoma. Am J Ophthalmol. 120:671–673. 1995. View Article : Google Scholar : PubMed/NCBI
26	Cho BJ and Yu HG: Risk factors for intraocular involvement in patients with primary central nervous system lymphoma. J Neurooncol. 120:523–529. 2014. View Article : Google Scholar : PubMed/NCBI
27	Akiyama H, Takase H, Kubo F, Miki T, Yamamoto M, Tomita M, Mochizuki M, Miura O and Arai A: High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma. Cancer Sci. 107:1458–1464. 2016. View Article : Google Scholar : PubMed/NCBI
28	Frenkel S, Hendler K, Siegal T, Shalom E and Pe'Er J: Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience. Br J Ophthalmol. 92:383–388. 2008. View Article : Google Scholar : PubMed/NCBI
29	Isobe K, Ejima Y, Tokumaru S, Shikama N, Suzuki G, Takemoto M, Tsuchida E, Nomura M, Shibamoto Y and Hayabuchi N: Treatment of primary intraocular lymphoma with radiation therapy: A multi-institutional survey in Japan. Leuk Lymphoma. 47:1800–1805. 2006. View Article : Google Scholar : PubMed/NCBI
30	Tropinskaya OF, Vetlova ER, Serova NK, Golanov AV and Fil'Chenkova NA: Radiotherapy of primary intraocular lymphoma associated with primary central nervous system lymphoma. Zh Vopr Neirokhir Im N N Burdenko. 80:74–81. 2016.(In English, Russian). View Article : Google Scholar : PubMed/NCBI
31	Berenbom A, Davila RM, Lin HS and Harbour JW: Treatment outcomes for primary intraocular lymphoma: Implications for external beam radiotherapy. Eye. 21:1198–1201. 2007. View Article : Google Scholar : PubMed/NCBI