Prognostic impact of intraocular involvement in primary CNS lymphoma: experience from the G-PCNSL-SG1 trial

Kreher, Stephan; Strehlow, Felicitas; Martus, Peter; Roth, Patrick; Hertenstein, Bernd; Röth, Alexander; Birnbaum, Tobias; Griesinger, Frank; Rauch, Michael; Kanz, Lothar; Thiel, Eckhard; Korfel, Agnieszka

doi:10.1007/s00277-014-2212-z

Cited by 22 publications

(16 citation statements)

References 21 publications

(18 reference statements)

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“…Grimm et al (14) reported that patients with PCNSL with and without intraocular involvement had similar PFS and OS rates; however, their study only included patients with ocular and parenchymal involvement at diagnosis. Kreher et al (15) demonstrated that patients with IOL had significantly inferior PFS and OS rates compared with non-IOL patients. In this study, not all patients received an ophthalmological evaluation.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…However, the search for other parameters supporting a prognostic discrimination has been widely futile except for some tissue markers including the expression of bcl-6 which has been associated with a favourable course of the disease (6). Furthermore, it has been reported that intraocular involvement in PCNSL may represent a negative prognostic indicator (7). In contrast, the relevance and application of minimally invasive biomarkers such as blood-borne patterns (e.g.…”

Section: Introductionmentioning

confidence: 99%

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Roth

Keller

Hoheisel

et al. 2015

European Journal of Cancer

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Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3months and was compared to 20 LTS patients with a median OS of 55months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients. Here we characterized microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analyzed by next generation sequencing.The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS.Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal AUC above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time PCR in a validation cohort consisting of 20 STS and LTS patients.In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients.

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“…However, single site involvement of either eye or CNS has a better prognosis than the double site involvement (PVRL and PCNSL) (71,96). The 5-year survival rate is higher in patients with isolated PVRL than in those with CNS involvement (71,82).…”

Section: Pvrl Prognosismentioning

confidence: 99%

“…However, the duration of complete remission did not differ between patients with and without CNS involvement (71). Kreher reported that the median progression-free survival in the PCNSL patients with intraocular involvement (3.5 months) was shorter than the ones without PVRL (8.3 months) (96). That is, intraocular involvement at diagnosis of PCNSL was an independent negative prognostic indicator for the progression-free survival and overall survival (96).…”

Section: Pvrl Prognosismentioning

confidence: 99%

“…Kreher reported that the median progression-free survival in the PCNSL patients with intraocular involvement (3.5 months) was shorter than the ones without PVRL (8.3 months) (96). That is, intraocular involvement at diagnosis of PCNSL was an independent negative prognostic indicator for the progression-free survival and overall survival (96). Local ocular therapy could improve disease control in PCNSL patients but may have no effect on the overall survival.…”

Section: Pvrl Prognosismentioning

confidence: 99%

See 1 more Smart Citation

Case 01-2017—Primary vitreoretinal lymphoma (PVRL): report of a case and update of literature from 1942 to 2016

2018

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Primary vitreoretinal lymphoma (PVRL), as a subset of primary central nervous system lymphoma (PCNSL), is a rare and fatal ocular malignancy. Most PVRL masquerades as chronic posterior uveitis, which makes the clinical diagnosis challenging. Vitreous cells, subretinal lesions and imaging techniques are essential for clinical diagnosis. Importantly, cytopathology/histopathology identification of malignant cells is the gold standard for the diagnosis of PVRL. In addition, molecular detection of immunoglobulin heavy chain (IgH) or T cell receptor (TCR) gene rearrangements, immunophenotyping for cell markers, and cytokine analysis of interleukine-10 elevation are often used as adjunct procedures. Current management of PVRL involves local radiation, intravitreal chemotherapy (methotrexate and rituximab), with or without systemic chemotherapy depending on the involvement of non-ocular tissues. In cases with concomitant PCNSL, systemic high-dose methotrexate/rituximab based therapy in conjunction with local therapy, whole brain radiotherapy and/or autologous stem cell transplantation is considered. Although PVRL normally responds well to initial treatment, high rates of relapse and CNS involvement usually lead to poor prognosis and limited survival. A professional team of medical experts in ophthalmologists, ocular pathologists, neuro-oncologists and hemato-oncologists is essential for optimizing patient management.

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Prognostic impact of intraocular involvement in primary CNS lymphoma: experience from the G-PCNSL-SG1 trial

Cited by 22 publications

References 21 publications

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

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

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Case 01-2017—Primary vitreoretinal lymphoma (PVRL): report of a case and update of literature from 1942 to 2016

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