Tuesday, December 9, 2008

Recurrent GBM (Resident Report)

KC presented a case of recurrent GBM after concurrent RT/TMZ.

Primary Treatment Roundup:
1. Reviewed data from the Stupp Trial from the EORTC reviewing, improvement of 2yr OS from 8% to 26% (SS) with the addition of TMZ with RT in primary treatment after maximal safe resection.  

2. MGMT methylation status was reviewed, showing that methylation status was associated with improved survival with concurrent TMZ.  MGMT methylation silences the MGMT gene product, which repairs TMZ damage.

Duke approach to primary treatment: 
50.4 Gy 1.8Gy QD preop T2 with 2cm margin 
boost to 59.4 Gy primary postop T1 + contrast with 1.5cm margin.
all with concurrent TMZ and adjuvant TMZ afterwards.
most failures still occur within the treated field

Salvage Treatment Roundup:
1. TMZ was shown with multiple retrospective trials to not show great response.
Other cytotoxics (CCNU and derivative, Platinums) also do not show great responses.

2. EGFR inhibitors (TKIs) also under active review.  EGFR is amplified in ~50% of GBMs
JCO 22:133-142 gefitinib median EFS 8.1 wks, no radiographic response
PASCO 22L1502-55 EGFR TKI PR rate 6-25%
Imatinib + HU for PDGFR (Reardon JCO 2005): PFS @ 6mo 27%, radiographic response 9%

3. VEGF inhibition: promising due to high VEGF levels and angiogenesis in GBMs
JCO 2007 Vrendenburgh Phase II 35pt, irinotecan + bevacizumab (PMI17947719)
6mo OS 77%, 6mo PFS 46%, 57% PR, Median PFS 24wks, 1 yr OS 37%

CW comments that caution should be used in interpreting radiographic response with VEGF modulators given that bev can normalize vasculature and therefore reduce enhancement on MRI without necessarily having an effect on the actual tumor.

RT for Recurrent GBM
1.  Mayer IJROBP 2008: reirradiation of the brain.  
Necrosis at NTD>100Gy (normalize to 2Gy fractions)
Interval made little difference (though this is a limited study)

2. Combs JCO 2005
172 retrospective of FSRT to 36Gy in 2Gy fx, low rates of necrosis

3. Combs ACS 2005
SRS to 15 GY median OS 10mo after SRS
no Grade III or greater toxicity

4.  Cho IJROBP 1999
46treated with SRS 17Gy, 25 FSRT (37.5Gy/15fx)
11 mo SRS vs 12 mo FSRT
increased late complications in SRS group

5. Kong ACS 2008
prospective study of 114 pts treated with SRS after failure from RTCT
median 16Gy dose

6. ASTRO evidence based review 2005 -
no phase III data for salvage SRS
median survival after salvage SRS 6-12mo
historical control is ~7mo
no data on QOL
80-85% still die with local failure
for FSRT also no real difference in FSRT vs SRS detectable

Case resolution:  recurred radiographically at 20mo
15Gy with 5 dynamic conformal arcs, to the 100% isodose line
conformality index 1.8
maximum tumor dose 17.3Gy
Pt doing well at 1 month follow up

Attending comments: JK states that it is reasonable to treat a nodular recurrence of GBM with SRS.  Prospective, systematic study, with QOL measurements is clearly needed.  FSRT may be used in larger recurrences. Future directions may be with concurrent targeted therapies.  Also he comments that MD Anderson work suggests that bev after SRS may reduce adverse events secondary to edema after SRS (work from metastatic disease).

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