2. Epidemiology
Brain, leptomeninges, eyes, or spinal cord without evidence of systemic
disease.
4 % of newly diagnosed primary CNS tumors.
45 - 65 years. Median age at diagnosis in the fifth decade.
Men and women are equally affected.
3.
4. Pathogenesis
Whether PCNSL arises inside or as transformed B cells originating outside the
brain is unclear.
Functional lymphatic vessels are present in the dural venous sinuses but brain
parenchyma itself lacks classic lymphatics and normally contains very few
lymphocytes.
Why lymphomas arise???
5. Pathogenesis
The observation that systemic dissemination of PCNSL is rare suggests that the
cells of origin in PCNSL may be derived from neoplastic lymphocytes that are
eradicated from the periphery by an intact immune system, but which are able
to survive in an immunologically aberrant CNS.
Highly selective neurotropism.
Facilitated through the expression of specific cell-surface adhesion molecules,
CD44,CD18 and various chemokine receptors (eg. CXCL).
6. Pathogenesis
Immunoglobulin variable heavy (IgHV) gene analysis suggest origin from
germinal B cells.
However, immunohistochemical evaluation suggests that PCNSL are derived
from postgerminal center B cells.
7. Gross pathology
Single or multiple hemispheric masses with a "fish flesh" consistency are
typical.
In contrast to astrocytomas, lymphomas tend to be relatively well demarcated
rather than diffusely infiltrating lesions.
Most are solid, pale lesions with occasional necrosis and small haemorrhagic
foci.
Large confluent areas of frank necrosis and gross intratumoral hemorrhage are
more common in AIDS related PCNSLs
8.
9. Microscopic Features
Highly cellular tumor.
Large atypical cells with large round to irregular nuclei with prominent nucleoli
are typical.
MIB-1 is high, often exceeding 50% (significantly higher than with
glioblastoma).
"Angiocentric" clustering.
10.
11. Microscopic Features
Majority of DLBCLs are positive on CD20 and CD45 immunostaining.
“Sentinel" lesions.
Even small doses of corticosteroids can induce striking apoptosis in PCNSLs.
Steroid treatment preceding biopsy can obscure the diagnosis of PCNSL in up
to 50% of cases.
13. Clinical presentation
Focal Neurological Deficit – 70 %
Neuropsychiatric symptoms – 43 %
Signs of raised ICT – 33 %
seizures – 14 %
ocular symptoms – 4 %.
20% - ocular involvement at the time of PCNSL diagnosis, bilateral in most
patients.
Bataille B, Delwail V, Menet E, et al. Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg 2000; 92:261.
14. Clinical presentation
IOL - floaters, blurred vision, diminished visual acuity, and painful red eyes.
Leptomeningeal involvement - 16% to 41%.
Headaches, CN palsies, meningismus, cervical/lumbar radiculopathies, and
hydrocephalus.
15. Clinical presentation
FND include aphasia, hemiparesis, ataxia with occasional CN palsy.
Neuropsychiatric changes include apathy, depression, slowed thinking, and
confusion.
Infiltration of the walls of the third ventricle produces SIADH, DI, hyposexuality,
hyperphagia, and psychotic thought changes.
16. Clinical presentation
When lymphoma invades the cranial or peripheral nerve roots
('neurolymphomatosis'), migratory pain syndromes emerge.
Isolated disorders of the fifth or seventh cranial nerves are often confused with
trigeminal neuralgia or Bell's palsy.
Painless polyneuropathies or involvement of a single nerve are rare.
17. Clinical presentation
The rare spinal cord lesions - discrete intramedullary nodules that may be
single or multiple.
Lower cervical or upper thoracic regions.
18. Clinical presentation
The mean period between onset of symptoms and the diagnosis of PCNSL is 3
months in immunocompetent patients and 2 months in those with AIDS.
The pace of neurological decline at presentation is variable.
19.
20. AIDS related CNS lymphoma
PCNSL accounts for upto 15% of NHL in HIV patient compared with only 1% of
NHL in general population.
Incidence in HIV-infected patients is 2 – 6 % (at least 1000 times higher than in
the general population ).
CD4 < 50 cells/microL.
21. AIDS related CNS lymphoma
Characterized by confusion, lethargy, memory loss, hemiparesis,
aphasia, and/or seizures that have usually been present for less than three
months.
More likely to present with mental status changes and seizures (50 vs 35 %).
Less likely to have increased ICP (14 vs 32 % ).
The pathogenesis of PCL is strongly related to Epstein-Barr virus infection.
22. Imaging
Contrast-enhanced MRI of the brain is the preferred.
As isolated spinal cord involvement is rare (1% of cases), spinal imaging is
indicated only in patients with myelopathy or suspected diffuse meningeal
dissemination.
Contrast-enhanced CT of the chest, abdomen, and pelvis or PET-CT is generally
recommended in patients with suspected PCNSL to look for an extracranial
source of disease.
23. Radiographic features
50 to 70 % of immunocompetent patients with PCNSL develop solitary lesions.
Periventricular lesions (eg, thalamus, basal ganglia, and corpus callosum) are
most common (60 %).
It is followed by lesions in the frontal, parietal, temporal, and occipital lobes in
20, 18, 15, and 4 % of patients, respectively.
Bataille B, Delwail V, Menet E, et al. Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg 2000; 92:261.
24. Radiographic features
The borders are sharply circumscribed in the majority of lesions (87 %), but
may be ill defined (15 %).
Although mild surrounding edema is present in the majority of cases, it is
usually less profound than metastatic foci of carcinoma.
Calcification, necrosis, cystic appearance, and ring enhancement are
uncommon except in Immunocompromised patients.
25. CT findings
Isodense to hyperdense on CT.
Enhance homogeneously after contrast administration.
26.
27.
28. MR findings
Over 3/4 of DLBCLs in immunocompetent patients are iso or slightly
hypointense compared with gray matter on T1WI and isointense on T2WI.
FLAIR signal is variable but usually iso or hyperintense.
Microhaemorrhages with intratumoural "blooming" on GRE in 5-8% of cases,
but gross haemorrhage is uncommon unless the patient is
immunocompromised.
29. MR findings
Because of their high cellularity, over 95% of PCNSLs show mild to moderate
diffusion restriction with low ADC values.
Nearly all PCNSLs in immunocompetent patients enhance. Solid homogeneous
or mildly heterogeneous enhancement is common; ring enhancement is rare.
MRS is nonspecific, with elevated choline, reduced NAA and myoinositol, and
prominent lipids.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39. Role of FDG-PET
In a study of 49 patients who had a body PET for staging of PCNSL, systemic
lymphoma was identified in 7 % of newly diagnosed patients and 27 % of
patients with relapsed PCNSL.
For NL, conventional brain and spine MRI may be normal. Focused MRI of
involved roots with coronal cuts are required. FDG-PET is slightly more sensitive
than MRI in the evaluation of suspected NL.
Mohile NA, Deangelis LM, Abrey LE. The utility of body FDG PET in staging primary central nervous system lymphoma. Neuro Oncol 2008; 10:223.
40. Radiological differential diagnosis
The major differential diagnosis of PCNSL is glioblastoma (GBM).
Both tumours often cross the corpus callosum, haemorrhage and necrosis are
rare in PCNSL.
Enhancement in immunocompetent patients with PCNSL is strong and
relatively homogeneous, whereas a peripheral ring pattern is more typical of
GBM.
DWI and MRS is helpful.
41. Radiological differential diagnosis
The second most common differential diagnosis of PCNSL is metastasis.
Lymphomatosis cerebri can mimic infectious or autoimmune inflammatory
encephalitis, microvascular disease, toxic-metabolic processes, diffusely
infiltrating glioma. Callosal involvement favours lymphomatosis cerebri.
50. AIDS related PCNSL
Multiple lesions are more frequent and larger areas of necrosis.
Intratumor haemorrhage is common.
Enhancement is variable but often mild. Ring enhancement surrounding a
nonenhancing core of necrotic tissue is typical.
51. AIDS related PCNSL
Lesions that involve the corpus callosum, periventricular, or ependymal areas
favours lymphoma.
< 10% of lymphomas involve the posterior fossa.
Lesions that are more than 4 cm in size favours Lymphoma.
PCL and toxoplasmosis usually produce a mass effect on CT or MRI. In one
series of HIV-infected patients with focal brain lesions, the probability of
progressive multifocal leukoencephalopathy was 81 percent among those
without a mass effect
Antinori A, Ammassari A, De Luca A, et al. Diagnosis of AIDS-related focal brain lesions: a decision-making analysis based on clinical and
neuroradiologic characteristics combined with polymerase chain reaction assays in CSF. Neurology 1997; 48:687
52.
53.
54.
55.
56.
57. Differential diagnosis
In immunocompromised patients, the major D/D of PCNSL is toxoplasmosis.
A solitary ring-enhancing lesion is most often lymphoma, whereas multiple
lesions are more characteristic of toxoplasmosis.
An "eccentric target" sign on T1 contrast is suggestive of toxoplasmosis.
Periventricular location/ subependymal spread – Lymphoma
Involvement of basal ganglia, thalamus, Grey-white matter junction -
Toxoplasmosis
61. CSF analysis
Presence of malignant lymphoid cells in up to 40 % of patients with PCNSL.
Flow cytometry may increase the sensitivity of CSF cytological analysis
Elevated protein concentration, lymphocytic predominant pleocytosis , glucose
concentration is usually normal, but may be lowered in the presence of
leptomeningeal disease.
62. CSF analysis
Immunohistochemical studies to establish monoclonality.
PCR analysis with consensus primers to the V and J regions of the
immunoglobulin heavy-chain used to detect clonal rearrangements.
Sensitivity and specificity of PCR is remained to be established.
63.
64.
65. CSF in AIDS related PCNSL
Positive cytological findings and/or PCR detection of Epstein-Barr virus DNA in
the CSF may establish the diagnosis of PCNSL in AIDS patients and obviate the
need for a biopsy procedure.
Positive results on CSF cytology - 23 %
PCR for EBV analysis of CSF has a sensitivity of 80 to 90 %, and a specificity that
approaches 100 %.
Plebani A, Pinzani R, Vago L, et al. Epstein-Barr virus DNA in the cerebrospinal fluid of an HIV patient with primary cerebral lymphoma. Eur J Pediatr
1998; 157:291.
66. Ocular Evaluation
Slit-lamp examination in all suspected of having PCNSL or the PIOL variant.
A cellular infiltrate in the vitreous, with or without subretinal infiltrates, is
typically seen in patients with ocular lymphoma.
Vitrectomy may establish the diagnosis of PCNSL by demonstrating malignant
lymphocytes in the eye.
67. Stereotactic needle biopsy
Diagnostic procedure of choice for PCNSL if there is no evidence of ocular or
CSF involvement.
The reason for this is twofold:
1. Patients do not benefit clinically from the surgical resection of PCNSL.
2. Frequent periventricular location increases the risk of surgical complications.
Target the center of the suspected lesion.
72. Steroid effect on PCNSL
Marked reduction or even disappearance of the tumor (“disappearing” or
“ghost” tumor) in at least 40% cases.
Invariable recurs within a few months and becomes poorly responsive to a
second treatment with steroids.
Steroid-induced responses also increase the risk of a non-diagnostic vitreal or
brain biopsy
Can also alter the CSF analyses (cytology and protein determination)
Caterina Giannini, Ahmet Dogan, Diva R. Salomão; CNS Lymphoma: A Practical Diagnostic Approach, Journal of Neuropathology & Experimental Neurology, Volume
73, Issue 6, 1 June 2014, Pages 478–494
73. Steroid effect on PCNSL
Loss of contrast enhancement on imaging.
‘‘Vanishing phenomenon’’ is not necessarily pathognomonic for PCNSL.
(demyelinating disease, sarcoidosis and renal cell carcinoma).
It should not be administered unless there is symptomatic and/or life-
threatening tumor-associated mass effect.
Caterina Giannini, Ahmet Dogan, Diva R. Salomão; CNS Lymphoma: A Practical Diagnostic Approach, Journal of Neuropathology & Experimental Neurology,
Volume 73, Issue 6, 1 June 2014, Pages 478–494
74. Treatment
Highly sensitive to both radiation and selected chemotherapeutic agents.
Induction and consolidation phases.
The goal of induction chemotherapy is a radiographic complete response (CR),
is achieved in over half of patients with MTX-based therapy.
Consolidation involves additional treatment to reduce recurrence rates,
improve overall survival rates, and potentially cure this disease.
Khê Hoang-Xuan, Eric Bessell et al., Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for
Neuro-Oncology, Lancet Oncol 2015; 16: e322–32
75. Induction Chemotherapy
High-dose methotrexate based chemotherapy ( 3.5-8 g/m2 ) – 1st line
Alone vs Combination
MTR regimen ( MTX, temozolomide, rituximab ). Median progression-free
survival (PFS) was 2.4 years.
MPV regimen ( MTX, procarbazine, vincristine ). Median progression-free and
overall survival was 3.3 and 6.6 years, respectively.
Khê Hoang-Xuan, Eric Bessell et al., Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for
Neuro-Oncology, Lancet Oncol 2015; 16: e322–32
76. Chemotherapy
MTX,cytarabine regimen.
MTX, cytarabine, thiotepa, rituximab
MTX monotherapy. Median progression-free and overall survival times of 12.8
and 23+ months, respectively.
Khê Hoang-Xuan, Eric Bessell et al., Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for
Neuro-Oncology, Lancet Oncol 2015; 16: e322–32
77. Endpoint of induction therapy
CR - Complete response
PR - Partial response
PD - Progressive disease
SD - Stable disease
The median number of doses of MTX required to achieve CR is approximately
6 to 8 in most studies. Sometimes it might go to 10-12 cycles.
Khê Hoang-Xuan, Eric Bessell et al., Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for
Neuro-Oncology, Lancet Oncol 2015; 16: e322–32
78. Consolidation therapy
Half of patients with PCNSL who achieve a CR will relapse within five years.
Nonmyeloablative chemotherapy and high-dose chemotherapy with
autologous HCT are the two main strategies.
WBRT remains an alternative consolidation approach in younger patients,
particularly those with contraindications to further chemotherapy.
Optimal consolidation approach is not known for elderly.
Khê Hoang-Xuan, Eric Bessell et al., Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for
Neuro-Oncology, Lancet Oncol 2015; 16: e322–32
79. Consolidation therapy
High-dose carmustine/thiotepa plus autologous HCT with or without WBRT
(estimated survival rates at two and five years were 81 and 70 percent,
respectively, and median survival was approximately 8.5 years ).
Khê Hoang-Xuan, Eric Bessell et al., Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for
Neuro-Oncology, Lancet Oncol 2015; 16: e322–32
80. Radiation therapy
Extremely sensitive but less used now.
WBRT in a dose of 40-45Gy with 1.8 – 2Gy dose per fraction is advisable in
patients non responsive to chemotherapy.
Neurotoxicity - the high incidence of cognitive worsening and white matter
damage.
Reduced dose WBRT.
Khê Hoang-Xuan, Eric Bessell et al., Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for
Neuro-Oncology, Lancet Oncol 2015; 16: e322–32
81. Glucocorticoid
Initial response rates of PCNSL to corticosteroids can be as high as 70 %.
Improvement is usually transient, and the disease tends to recur within a few
months after discontinuation of these agents.
Can be used as a palliative therapy with WBRT who are not candidate for
chemotherapy.
82.
83.
84. Treatment of AIDS related PCNSL
No proven optimal therapy.
High dose MTX concurrently with steroids and potent HAART.
After resolution of mass effect, steroid can be tapered.
Radiotherapy is not much useful.
87. References
Neska-Matuszewska M et al., Differentiation of glioblastoma multiforme, metastases and
primary central nervous system lymphomas using multiparametric perfusion and diffusion MR
imaging of a tumor core and a peritumoral zone-Searching for a practical approach. PLoS One.
2018;13(1). Published 2018 Jan 17
Giannini, Ahmet Dogan, Diva R. Salomão; CNS Lymphoma: A Practical Diagnostic
Approach, Journal of Neuropathology & Experimental Neurology, Volume 73, Issue 6, 1 June
2014, Pages 478–494
Khê Hoang-Xuan, Eric Bessell et al., Diagnosis and treatment of primary CNS lymphoma in
immunocompetent patients: guidelines from the European Association for Neuro-Oncology,
Lancet Oncol 2015; 16: e322–32
www.uptodate.com
Osborn’s Brain ( 2nd edition )
Together, lymphoid neoplasms comprise the sixth most common group of CNS malignancies.
More than 95% are diffuse large B-cell lymphomas.
What is clearly evident is that lymphoma cells—regardless of whether they originate within or outside the brain—exhibit a distinct, highly selective neurotropism for the CNS microenvironment and its vasculature.
The high incidence of PCNSL in immunodeficient states strongly implicates the immune system in the pathogenesis of PCNSL.
Almost all PCNSL cells demonstrate IgHV genes that have high levels of somatic mutations and show intraclonal heterogeneity pointing towards their derivation from mutated germinal center B cells.
MIB 1 is cell proliferation marker. A marker of mitosis.
Most PCNSLs exhibit a distinct predilection for blood vessels,
with layering of tumor cells in and around vessels that extend
from these perivascular cuffs into the adjacent parenchyma. - "angiocentric" clustering
Occasionally, steroid-responsive multifocal demyelinating "sentinel" lesions that are indistinguishable from those seen in tumefactive MS or ADEM can be seen months or even several years before PCNSL is diagnosed.
This includes HIV infection, iatrogenic immune suppression, and congenital immune deficiency including ataxia-telangiectasia, Wiskott-Aldrich syndrome, severe combined and common variable immunodeficiencies.
Neuropsychiatric changes include apathy, depression, slowed thinking, and confusion attributed to the infiltration of white matter tracts by PCNSL lesions that involve the periventricular regions or the corpus callosum.
The pace of neurological decline at presentation is variable; some patients exhibit chronic visual symptoms that antedate the diagnosis by years, while for others, disease progression is highly aggressive.
As isolated spinal cord involvement is rare (3-4% of cases), spinal imaging is indicated only in patients with myelopathy or suspected diffuse meningeal dissemination.
Contrast-enhanced CT of the chest, abdomen, and pelvis or PET-CT is generally recommended in patients with suspected PCNSL to look for an extracranial source of disease.
Spinal disease can be detected by MRI.
Axial pre-contrast CT images (A) show hyperattenuating periventricular masses crossing the midline with surrounding oedema. Post-contrast CT images (B) demonstrate avid homogeneous enhancement of the lesions.
N acetyl aspartate
63-year-old female with primary CNS lymphoma.
single mass that infiltrates the splenium of corpus callosum [a relatively common location for primary CNS lymphoma] (arrow), abutting the third ventricle anteriorly.
The mass enhances homogeneously following gadolinium administration (B),
is relatively dark on T2 weighted images (C)
restricted diffusion on the diffusion weighted sequence (bright, D). The reader should note the relative lack of edema on flair studies.
Axial T1WI shows a mass ſt in the left basal ganglia that is mostly isointense with cortex.
T2WI in the same case shows that the mass is mixed iso- to hypointense.
ADC map shows that the mass exhibits mild to moderate restricted diffusion.
T1 C+ FS shows that the mass ſt enhances intensely and uniformly.
lesions in the basal ganglia and thalami that appear isointense with gray matter.
T2WI in the same case shows that the lesions appear isointense with gray matter, associated with some hyperintense peripheral edema.
Lesions enhance strongly and uniformly.
Restricted diffusion with low ADC. Peritumoral edema is hyperintense because of "T2 shine-through."
64y woman with altered mental status and increasing confusion.
Axial T1WI diffuse confluent hypointensity in both frontal lobes and the corpus callosum genu.
Axial T2WI shows confluent hyperintensity and gyral expansion of both frontal lobes with genu of corpus callosum.
Sagittal FLAIR in the same case shows infiltration and expansion of the corpus callosum.
DWI in the same case shows restricted diffusion throughout the periventricular WM.
56 yr old woman 20 days h/o behaviour abnormality without prior fever.
perivascular curvilinear enhancement perpendicular to the lateral ventricle following gadolinium administration.
Rapidly progressing dementia in the elderly and diffuse leukoencephalopathy on MRI should prompt the consideration of diffuse PCNSL
massively elevated lipid resonances are a hallmark of PCNSL in immunocompetentpatients.
markedly elevated Cho/Cr ratio, is greater in PCNSL than in high-grade astrocytomas.
Perfusion weighted MRI.The CBV map (C) shows the hyperperfused tumor core (white arrow, max rCBV = 2.9) and a large area of increased perfusion (yellow arrow, max rCBV = 2.25) within the peritumoral zone indicating neoplastic infiltration which is a feature differentiating GBM from a metastasis surrounded exclusively by a pure vasogenic edema.
Perfusion weighted MRI.The CBV map (C) shows the hypoperfused tumor core (max rCBV = 0.79) with the perfusion curve (D) returning above the baseline (red transverse line) which are typical perfusion characteristics of PCNSL.
highly perfused tumor (max rCBV = 17.9) and no hyperperfusion within the peritumoral zone (max rCBV = 0.78) typical for pure vasogenic edema.
CER – Contrast enhanced region
PTR – Peritumoral region
CECT scan shows necrosis and only faint rim enhancement ſt in this HIV-positive patient with PCNSL
T1WI shows T1 shortening due to subacute haemorrhage with more acute haemorrhage in the necrotic core of the lesion.
A)FLAIR in a 43y HIV+ man with ataxia shows a solitary right cerebellar lesion with surrounding edema and mass effect.
B)T1 Contrast in the same case shows a thick, irregular enhancing rim surrounding a core of necrotic nonenhancing tissue.
C)DWI shows diffusion restriction in the rim and lesion core.
Immunodeficiencyrelated DLBCL was found at surgery.
201Tl behaves like K+ and enters living cells via the Na+/K+ ATPase. It does not accumulate in necrotic/dead tissue and thus provides another method of potentially differentiating neoplastic from infectious lesions
There may be difficulty distinguishing between reactive and malignant cells or distinguishing reactive cells in the CSF from small cells of medulloblastoma as distinct from malignant B cells.
In such cases, immunophenotypic analysis using antibodies against lymphocytic antigens is particularly helpful in establishing the lymphoid origin and clonality of the malignant cells, when present, and to differentiate between B and T cell subtypes.
Demonstration of clonal immunoglobulin gene rearrangements can establish monoclonality of a lymphocyte population in the CSF and thus confirm the diagnosis of PCNSL.
CSF AT3 level cutoff – 1.2 g/ml.
PCR for JC virus – Good sensitivity and specificity.
PCR for toxoplasmosis – 50% sensitivity, 96-100% specifitivity.
PCR for CMV – 80% sensitivity and 90% specitivity.
The vitrectomy should be performed in the eye with the worst vision or the most severe vitritis. chorioretinal biopsy sampling or fine-needle aspiration of a subretinal lesion may be performed if virtrectomy fluid is negative.
Special handling of the specimen is required because lymphoma cells in the vitreous degenerate rapidly.
The pathologic evaluation and classification of PCNSL tumors is similar to that of tumors of systemic NHL.
For most patients with a good performance status (ie, Eastern Cooperative Oncology Group [ECOG] ≤3), we suggest using MTX-based combination regimen rather than MTX alone.
Older patients with borderline functional status may do better with MTX monotherapy.
We include rituximabin all regimens, except in rare cases of CD20-negative or T cell PCNSL.
A complete response (CR) is obtained if there is complete disappearance of all enhancing abnormalities on gadolinium-enhanced MRI and the patient has not received any corticosteroids for at least two weeks. Patients who had prior ocular involvement should have no evidence of active ocular lymphoma. Patients with previous CSF involvement should have negative CSF studies.
PR - no new sites of disease, at least a 50 percent decrease in the contrast-enhancing lesion seen on MRI compared with baseline, and a decrease in the vitreous cell count or retinal/optic nerve cellular infiltrate. CSF cytology may continue to show persistent malignant or suspicious cells, and patients may be receiving corticosteroid treatment.
Progressive disease(PD) - there is a more than 25 percent increase in the contrast-enhancing lesion seen on MRI, an increase in the vitreous cell count, progressive retinal or optic nerve infiltration, new lesions in an old site, or involvement of a new site of disease
Stable disease(SD)
WBRT remains a reasonable salvage therapy in patients who have not responded adequately to induction chemotherapy. In addition, WBRT plus corticosteroids may be used for the palliation of patients who are not candidates for chemotherapy.
Reduced-dose WBRT consolidation in responding patients has been explored in phase II studies and appears to be associated with high response rates and decreased rates of neurotoxicity compared with higher-dose WBRT
TMZ - temozolomide
Radiotherapy - survival is 1-3 months from the time of presentation in untreated patients; the outcome is not substantially improved by radiation therapy, with reported median survivals of up to 3.5 months.
