Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Radiation Oncology Residency > Primary CNS lymphoma > Flashcards

Primary CNS lymphoma Flashcards

1
Q

What are the incidence and median age at Dx of PCNSL?

A

1,000 cases/yr of PCNSL; median age 55 yrs (immunocompetent) vs. 35 yrs (immunocompromised)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What % of primary brain tumors are PCNSL?

A

∼4%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the sex predilection, and how does it relate to

immunocompetency?

A

Immunocompetent pts: males > females (2:1)

AIDS pts: 95% males

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What risk factors are often associated with CNS lymphoma?

A

Immunodeficiency (congenital or acquired) and EBV infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What type of non-NHL is most often associated with PCNSL?

A

DLBCL is most often associated with PCNSL.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What % of PCNSL has ocular involvement?

A

15% of PCNSL has ocular involvement (vitreous, retina, choroid > optic nerve) that is typically bilat.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the most common genetic alteration seen in PCNSL?

A

The most common genetic alteration in PCNSL is the gain of chromosome 12 (12p12–14), which corresponds to the amplification of MDM2 to enhance p53 suppression.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

If the pt presents with ocular lymphoma, what % later develop CNS involvement?

A

75% of pts who present with ocular lymphoma develop CNS involvement.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

With what is orbital lymphoma often associated?

A

Systemic NHL is often associated with orbital lymphoma.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What % of pts diagnosed with PCNSL present with isolated SC/meningeal involvement?

A

<5% of pts present with isolated SC/meningeal involvement.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What proportion of pts diagnosed with PCNSL present with CSF involvement?

A

One-third of pts present with CSF involvement.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What % of pts present with PCNSL but have a negative systemic lymphoma workup?

A

Nearly all pts (>95%) who present with PCNSL have a negative lymphoma workup, so if lymphoma is found outside the CNS, it is NHL with involvement of the CNS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the high-risk features of systemic NHL that increase the risk of CNS mets?

A

Burkitt, lymphoblastic lymphoma, immunocompromised pt, BM+, parameningeal presentation (NPX, PNS), and testicular relapse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What % of pts present with multifocal Dz?

A

Immunocompetent pts: 50%

AIDS pts: 100%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What % of pts with grossly unifocal Dz are actually microscopically multifocal?

A

> 90% of pts with grossly unifocal Dz are microscopically multifocal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What % of AIDS pts develop CNS lymphoma?

A

2%–13% of AIDS pts develop CNS lymphoma. Invariably all are EBV+.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What has happened to the incidence of PCNSL over the past 30 yrs?

A

There has been a dramatic increase (3-fold) in immunocompetent and immunocompromised PCNSL pts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

In what regions of the CNS does PCNSL arise?

A

Brain, SC, leptomeninges, and globe (retina, vitreous)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What virus has been associated with PCNSL?

A

EBV has been associated with PCNSL (60% of immunocompromised cases).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Are B cells normally found in the CNS?

A

No. They develop as part of the pathologic process of PCNSL.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the more radioresistant NHL: intracranial or extracranial?

A

Intracranial. Per RTOG 8315, pts rcvd 40 Gy WBRT + 20 Gy boost and 25 of 41 pts (61%) failed in the brain.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What % of PCNSLs are supratentorial?

A

The majority of PCNSLs (75%) are supratentorial.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

With which CNS Sx do pts with PCNSL present?

A

Focal neurologic deficits (70%), neuropsychiatric/personality change (frontal
lobe involvement [43%]), ↑ ICP ([33%] HA, n/v, CN VI deficit, blurred vision), seizures, leg weakness, urinary incontinence/retention, and ocular Sx (blurry vision)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

With which systemic Sx do pts present?

A

Fever, night sweats, and weight loss (80%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

All PCNSLs are what stage? What type of NHL?

A

All PCNSLs are stage IE. PCNSL is considered an extranodal NHL.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What brain location and specific structures are commonly involved?

A

The #1 location is the frontal lobe, often the deep white matter and frequently periventricular (↑ CSF spread).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are considered deep structures of the brain according to the International Extranodal Lymphoma Study Group (IELSG)?

A

Corpus callosum, basal ganglia, brainstem, and cerebellum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How is the Dx of ocular lymphoma made?

A

The Dx of ocular lymphoma is made by slit lamp exam and vitrectomy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What infectious etiology is often confused with CNS lymphoma?

A

Toxoplasmosis is the infectious etiology often confused with CNS lymphoma.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the DDx for PCNSL?

A

Secondary metastatic lymphoma, other primary brain tumors, mets, abscess, hemorrhage, multiple sclerosis, sarcoidosis, and toxoplasmosis in AIDS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the 1st step if a pt has a brain MRI suggestive of lymphoma?

A

Bx of brain lesion, least invasive approach. Consider LP, if safe and would not delay Tx or diagnostic process, to obtain CSF (15–20 mL to increase diagnostic yield). If the MRI and CSF show unequivocal evidence of PCNSL,
brain Bx may be deferred (per NCCN). Do not initiate steroids, if possible, prior to diagnostic procedure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What do you do if the Bx for suspected PCNSL is nondiagnostic?

A

If the pt rcvd steroids prior to the Bx, then D/C the steroids and re-Bx when Dz progresses. If no steroids were given, can re-Bx or workup for other Dx.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the workup of a pt with a new Dx of CNS lymphoma (per NCCN 2018)?

A

Ophthalmic slit lamp exam to r/o ocular involvement, LP if safe, MRI spine if symptomatic or +CSF, CBC, CMP, LDH, HIV status, PET/CT or contrastenhanced
body CT, consider BM Bx, consider testicular US (men >60 yo)

34
Q

What imaging studies should be performed?

A

MRI brain (MRI spine if Sx or CSF+), contrast-enhanced body CT or PET/CT

35
Q

How does CNS lymphoma appear on MRI?

A

Indistinct fluffy borders, periventricular location common, T1 enhancement with gadolinium, and ring enhancement (d/t central necrosis, often seen in AIDS), less edema than would be expected for similar-sized glioma or mets

36
Q

When is PCNSL more likely to be multifocal?

A

PCNSL is more likely to be multifocal when the pt is immunocompromised (50%–80% of such pts).

37
Q

What chemical abnormalities are seen in the CSF of pts with CNS lymphoma?

A

↑ Protein (85%), ↓ glucose (33%), ↑ LDH, ↑ β2-microglobulin

38
Q

What additional tests are necessary for AIDS pts with a possible Dx of CNS lymphoma?

A

Toxoplasmosis titer (r/o this and other opportunistic infections) and BM Bx

39
Q

How can the Dx of PCNSL be most definitively established?

A

Bx brain/globe or CSF sampling

40
Q

What are the 5 poor prognostic factors for PCNSL according to the IELSG?

A 
Poor prognostic factors for PCNSL:
1. Age >60 yrs
2. ECOG PS >1
3. Elevated LDH
4. Elevated CSF protein
5. Deep brain involvement (periventricular, basal ganglia, brainstem, cerebellum)
(Fererri AJ et al., JCO 2003)
41
Q

What is the 2-yr OS for pts with 0–1, 2–3, and 4–5 factors?

A

2-yr OS for these pts is 80%, 50%, and 15%, respectively. (Fererri AJ et al., JCO 2003)

42
Q

What are other prognostic factors for PCNSL?

A

Poor response to chemo, AIDS, and multifocality

43
Q

Who are considered “good-risk” immunocompromised pts with PCNSL?

A

Non-HIV immunosuppression and HIV+ with CD4 >200

44
Q

What is the management paradigm for an immunocompetent pt with PCNSL and KPS ≥40?

A

PCNSL management paradigm: high-dose Mtx (good CNS penetration) based regimen. If CR: consider: high-dose chemo with stem cell rescue, high-dose cytarabine +/– etoposide, or low-dose WRT.
If no CR: WBRT, or consider high-dose cytarabine +/– etoposide, or best supportive care.

45
Q

What is the management paradigm for a KPS <40?

A

Give steroids. If KPS improves, chemo, otherwise WBRT (24–36 Gy WBRT then boost to 45 Gy). (NCCN 2018)

46
Q

What is the 1st intervention in a symptomatic pt after Bx?

A

The use of high-dose steroids is the 1st intervention in a symptomatic pt after Bx.

47
Q

If a pt is suspected of harboring PCNSL, why should steroids not be started right away before obtaining a Bx?

A

Tumor regression (in 90%) with subsequent Bx yielding nondiagnostic results; Bx 1st → start of steroids (upfront steroids only for unstable pts)

48
Q

How does the RT response differ b/t PCNSL and other types of extranodal NHL?

A

PCNSL is very radioresistant (5-yr OS is 4%). Extranodal NHL response is 90%.

49
Q

How did the IELSG determine the prognostic groups that may predict for better survival?

A

Fererri AJ et al.: 378 pts from 1980–1999, HIV– with CNS lymphoma. All were treated with various regimens (+/– chemo, +/– RT). (JCO 2003)

50
Q

How do survival outcomes differ b/t CRT and RT alone?

A

MS is ∼44 mos (CRT) vs. ∼10–18 mos (RT alone). 5-yr OS is 30% (CRT) vs. 5% (RT alone).

51
Q

What % of pts are long-term survivors?

A

∼15%–20% long-term survival in contemporary clinical trials of Mtx-based chemo (+/– RT).

52
Q

What is the outcome of pts with ocular lymphoma?

A

The outcome of pts with ocular lymphoma is uniformly fatal. MS is only 6–18 mos.

53
Q

Is cyclophosphamide HCl/doxorubicin/Oncovin/prednisone (CHOP) effective against PCNSL? Is cyclophosphamide
HCl/doxorubicin/Oncovin/dexamethasone (CHOD) effective?

A

No. There is ineffective blood–brain barrier penetration. 3 RCTs, including RTOG 8806 (Schultz C et al., JCO 1996), demonstrated no benefit of CHOP
or CHOD.

54
Q

What pts should be considered for WBRT after chemo and to what dose?

A

This should be decided based on the response to chemo. In general should be given to younger pts, as WBRT may increase neurotoxicity especially in pts
>60 yrs. The dose depends on the response. For CR after chemo, give WBRT 23.4 Gy in 1.8 Gy fx. If

55
Q

What were the results of the phase II trial on R-MPV f/b reduced-dose consolidative WBRT and cytarabine (Morris PG et al., JCO 2013)?

A

This was a multicenter phase II study of 52 pts receiving induction rituximab (Rituxan), Mtx, procarbazine, and vincristine (R-MPV) for 5–7 cycles, f/b reduced dose WBRT (23.4 Gy) for a CR or standrad WBRT (45 Gy) for
nonCR. 60% had CR and rcvd reduced dose WBRT, with 3-year OS of 87% and 2-yr PFS of 77%. There was min neurotoxicity.

56
Q

Which study demonstrated that an RT boost is not beneficial for PCNSL?

A

RTOG 8315 (phase II): WBRT 40 Gy → CD to 60 Gy. MS was 11.5 mos. 80% failed in the boost field.

57
Q

What does the Memorial MSKCC data demonstrate on the use of highdose Mtx + WBRT and the relation of age to developing neurotoxicity

A

MSKCC data: phase II, 52 pts. MS was 60 mos. High-dose Mtx × 5 cycles (3.5 g/m2) was Alt intrathecal Mtx (12 mg) → procarbazine/vincristine + WBRT 45 Gy → high-dose cytosine arabinoside (Ara-C) (intravenous 3 mg × 2). Of those aged >60 yrs, some did not rcv RT. Survival was the same b/t no RT vs. RT, but DFS was worse if there was no RT. Those >60 yrs who rcvd RT had ↑ risk of neurotoxicity (83%) vs. age <60 yrs (6%). With chemo
alone, only 1 pt developed neurotoxicity. (Abrey LE et al., JCO 2000)

58
Q

In the Abrey study, what was the response rate to pre-RT chemo?

A

CR 56% and PR 33% (ORR 89%). (Abrey LE et al., JCO 2000)

59
Q

In RTOG 9310, did 36 Gy (1.2 Gy bid) benefit PCNSL pts when compared to 45 Gy (conventional qd) WBRT?

A 
RTOG 9310 (Fisher B et al., J Neurooncol 2005): no difference in control and survival, but worse neurotoxicity (23% vs. 4%); prospective study of
Abrey chemo regimen → 45 Gy vs. 36 Gy bid (if CR to chemo) (63 pts rcvd 45 Gy, and 16 pts rcvd 36 Gy. MS was 37 mos).
60
Q

What were the results of RTOG 0227?

A 
RTOG 0227 (Glass J et al., JCO 2016) was a phase I/II study of induction chemo with Mtx, rituximab, and TMZ, f/b hyperfractionated WBRT (hWBRT; 36 Gy in 1.2 Gy bid) and subsequent TMZ. In phase I, 13 pts rcvd
increasing doses of TMZ, and in phase II, 53 pts were treated. 2-yr OS and PFS of 81% and 64%, respectively, were significantly improved compared to historical controls from RTOG 9310 (see above). 66% had G3/4 toxicity before hWBRT, and 45% had G3/4 toxicity attributed to hWBRT. Cognitive function and QOL improved/stabilized after hWBRT.
61
Q

What did the RCT of +/- consolidative WBRT by Thiel et al. show (JCO 2010)?

A

This was a multicenter, randomized phase III, noninferiority trial of 318 pts treated with high-dose Mtx + ifosfamide +/– WBRT. There was no OS
difference (32.4 mos WBRT vs. 37.1 mos no WBRT). There was improved PFS in the WBRT arm but neurotoxicity was more common in the WBRT
arm (49% vs. 26%).

62
Q

What are the CR rates with chemo and deferred RT after chemo?

A

Several phase II trials have tested this approach of chemo with deferred RT, with CR rates ranging from 42% to 61%, and OS from 14 to 55 mos.
However some pts did not achieve CR and need WBRT, and even among those with CR, ∼half relapse.

63
Q

In pts with failure after high-dose Mtx without prior RT, what are the Tx options?

A

If the response duration >12 mos, options include: re-treating with high-dose Mtx, other systemic therapy, high-dose therapy with stem cell rescue. If the
response duration <12 mos, WBRT or involved field RT with/without chemo, or consider high-dose therapy with stem cell rescue

64
Q

What is the typical response rate to salvage WBRT for pts failing initial chemo?

A

CR 37%–58% and PR 21%–37% (Nguyen PL et al., JCO 2005; Hottinger AF et al., Neurology 2007)

65
Q

What critical volumes need to be covered with WBRT?

A

The post retina and CNS down to C2 need to be covered.

66
Q

What volumes are treated with RT if the pt presents with an ocular primary?

A

WBRT to C2, + bilat orbits with opposed lats to 36 Gy → CD to WBRT + post retina to 45 Gy

67
Q

How should AIDS+ PCNSL be treated?

A

The optimal therapy has not been well defined. High-dose Mtx therapy with steroids and antiretroviral therapy has been shown to offer palliation for up to
12–18 mos. In very select pts, can consider rituximab plus high-dose Mtx. WBRT has historically been the standard Tx, which leads to CR rates of 20%–50%, but survival is still very poor, ∼3.5 mos.

68
Q

What was the Tx regimen in RTOG 93–10? What was the MS?

A

Intravenous/intrathecal Mtx/vincristine/procarbazine → WBRT to 45 Gy → intravenous cytarabine. MS was 3 yrs. (DeAngelis LM et al., JCO 2002)

69
Q

What options are there for leptomeningeal PCNSL?

A

Intrathecal Mtx or high-dose Mtx. Alternative therapies include slow release cytarabine, systemic chemo, or CSI to 36 Gy with a boost to 45–50 Gy.

70
Q

What is the Tx paradigm for ocular lymphoma?

A

Ocular lymphoma Tx paradigm: RT to 36 Gy or intraocular chemo

71
Q

What is the rationale for omitting WBRT in the elderly with PCNSL?

A

Neurotoxicity in older pts (Abrey LE et al., JCO 2000): 80% of pts >60 yo had neurocognitive defects after 45 Gy; 6% if <60 yo. Some pts >60 yo did not get WBRT and had similar OS (worse DFS with no WBRT, however).

72
Q

What is the WBRT dose for PCNSL after CR to chemo?

A

24–36 Gy. Consider omitting RT altogether if the pt is >60 yo.

73
Q

What is the WBRT dose for PCNSL after PR to chemo?

A

36–45 Gy WBRT; focal CD to gross Dz to 45 Gy

74
Q

What is 1 additional systemic option after RT, especially after PR to initial chemo?

A

Consolidation high-dose cytarabine +/- etoposide is an additional option after RT.

75
Q

What is the role of rituximab in PCNSL? How can it be incorporated, and what studies support its use?

A 
Can be used with Mtx/procarbazine/vincristine) as induction regimen →dose-reduced WBRT to 23.4 Gy if CR (45 Gy if PR) → Ara-C consolidation.
MSKCC data (Shah GD et al., JCO 2007): 2-yr OS, 67%, 2/3 pts had CR Morris PG et al., JCO 2013: 3-yr OS 87%, 60% had CR
76
Q

What is another consolidative option in pts with a CR to chemo?

A

High-dose chemo with stem cell rescue, based on several single-arm phase II studies. 1 multicenter phase II study (Illerhause G et al., Blood 2012) of 79
pts (<65 yrs) rcvd induction chemo with Mtx, cytarabine, thiotepa and rituximab → high-dose carmustine/thiotepa + auto HCT (only those without CR after HCT, n = 10, had WBRT). The CR was 27% after induction chemo
and 77% after HCT. The 2-year OS was 87%.

77
Q

What did RTOG 8315 investigate? What did it show?

A

RTOG 8315: RT alone/dose escalation (40 Gy + 20 Gy boost). There was high LR in the brain at 61% and significant neurotoxicity with higher doses.
(Nelson DF et al., IJROBP 1992)

78
Q

Which recent randomized international phase II study investigated the use of induction cytarabine for PCNSL? What did it find?

A

IELSG (Ferreri AJ et al., Lancet 2009): randomized to 4 cycles of Mtx vs. Mtx/cytarabine → WBRT. CR rates were 18% vs. 46% and ORR 40% and 69%, respectively.

79
Q

What regimen was used in CALGB 50202 and what were the results?

A

Mtx, TMZ, and rituximab (MT-R) f/b etoposide/cytarabine consolidation (EA), with no WBRT. CR is 66% with 2-yr PFS of 57%—comparable to previous regimens with WBRT. (Rubenstein JL et al., JCO 2013)

80
Q

What is the recommended radiographic f/u for PCNSL?

A

MRI q3 mos for 2 yrs, q6 mos for yrs 2–5, then annually (NCCN 2018

81
Q

What was the toxicity rate in the RTOG 93–10 study?

A

RTOG 93–10: 15% had severe delayed neurotoxicity (especially if >60 yo). (DeAngelis LM et al., JCO 2002)

82
Q

What was the Tx-related mortality for pts treated with chemo alone in the German trials?

A

In German trials, Tx-related mortality with chemo alone was 9%. PCNSL: results of a pilot and phase II study of systemic and intraventricular chemo with deferred radiotherapy. (Pels H et al., JCO 2003

Radiation Oncology Residency (44 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions