Page 162 - Haematologica Vol. 107 - September 2022

ARTICLE - Use of aqueous humor in VRL management
X. Wang et al.
cluded in this study; the line of treatment varied from first-line to third-line; and subset analyses were not per- formed because of the restricted cohort size. These limi- tations prevented a direct comparison of the efficacy of ibrutinib treatment between VRL and PCNSL patients; however, the findings should promote additional well-de- signed and comprehensive studies of the efficacy of ibrutinib in VRL patients in the future.
The evaluation of disease progression in VRL patients, un- like that of patients with solid tumors, relies mainly on eye examinations and patients’ visual acuities, which are subjective rather than quantitative. Our results suggest that the changes in AH/VF ctDNA allele frequencies were relatively concordant with IL-10 levels in AH/VF. It is known that IL-10 is a clinical marker of VRL,36,37 so AH ctDNA monitoring might be an efficient and quantitative tool to evaluate treatment responses in patients with VRL. In addition, we found that the early detection of CSF ctDNA might be an indication of brain involvement, sug- gesting that patients with positive CSF ctDNA require close monitoring. Of note, although CSF has been ac- cepted as a better surrogate than plasma for the molecu- lar profiling of brain tumors.38,39 the allele frequencies of CSF ctDNA-derived mutations were significantly lower than those of AH/VF-derived aberrations. Furthermore, mutations detected in CSF samples represented only a subset of AH/VF-borne mutations. That observation sug- gested that lymphoma was likely to be of an ocular origin in those patients, but considering that CSF has a much higher dilution volume than AH/VF, caution in the inter- pretation of disease origin is warranted.
Several limitations of this study should be noted. First, the cohort size was restricted due to the rarity of VRL, and thus, further validation in larger cohorts is warranted. Second, the volume of AH/VF samples available for cfDNA extraction varied between patients, but sample volumes were usually small, leading to a limited amount of cfDNA for NGS. Therefore, ctDNA sequencing with AH/VF bi- opsies was technically demanding. Lastly, the efficacy profile of ibrutinib in VRL and PCNSL requires further in- vestigation because of the heterogeneity and diverse
References
1. Chan CC, Rubenstein JL, Coupland SE, et al. Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium. Oncologist. 2011;16(11):1589-1599.
2. Buggage RR, Chan CC, Nussenblatt RB. Ocular manifestations of central nervous system lymphoma. Curr Opin Oncol. 2001;13(3):137-142.
3. Chan CC, Buggage RR, Nussenblatt RB. Intraocular lymphoma. Curr Opin Ophthalmol. 2002;13(6):411-418.
4. Soussain C, Malaise D, Cassoux N. Primary vitreoretinal
treatment conditions between cohorts in this study. However, our collective findings revealed the molecular heterogeneity of VRL and PCNSL, and highlighted the clinical utility of serial AH/VF ctDNA profiling for the di- agnosis and monitoring of VRL.
Disclosures
Xiaoxia W, YM, and QO are employees of Nanjing Geneseeq Technology Inc. The remaining authors have no conflicts of interest to declare.
Contributions
Xiaoxiao W and HH designed the study; Xiaoxiao W estab- lished the methodology; WS, YG, XC, and YH curated data; WS and Xiaoxia W performed the investigation; Xiaoxiao W, WS, YH, and YM performed the formal analysis; YG, YF, XC, QO, and DL validated the data; YF, Xiaoxia W and YM visualized the data; Xiaoxiao W and YM wrote the draft of the article; WS, YG, and QO edited the manuscript; DL ad- ministrated the project; HH acquired the funding. All authors read and agreed to the final version of the manu- script.
Acknowledgments
The authors would like to thank the patients and family members who gave their consent to presenting the data in this study, as well as the investigators and research staff involved in the study.
Funding
This study was supported by the National Science & Tech- nology Major Project (grant number: 2017ZX09304021).
Data-sharing statement
The human sequence data generated in this study are not publicly available due to patient privacy requirements but are available from the corresponding author upon reason- able request. Other data generated in this study are avail- able within the article and its Online Supplementary Data Files.
lymphoma: a diagnostic and management challenge. Blood.
2021;138(17):1519-1534.
5. Salomao DR, Pulido JS, Johnston PB, Canal-Fontcuberta I,
Feldman AL. Vitreoretinal presentation of secondary large B-cell lymphoma in patients with systemic lymphoma. JAMA Ophthalmol. 2013;131(9):1151-1158.
6. Coupland SE, Hummel M, Stein H, Willerding G, Jahnke K, Stoltenburg-Didinger G. Demonstration of identical clonal derivation in a case of "oculocerebral" lymphoma. Br J Ophthalmol. 2005;89(2):238-239.
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