Low Grade (I-II) Gliomas

Question 1

Early surgery or watchful waiting?

Answer 1

No prospective trials.
Jakola, Norwegian University Hospitals (JAMA 2012)
Hospital A: pts biopsied & observed (50% eventually got surgery).
Hospital B: pts underwent early resection.
5yr OS better with early surgery (60 vs 74%).

Question 2

After surgery, observe or RT?

Answer 2

(1) EORTC 22845 “Non-Believers Trial” (Lancet 2005), PRT
R immediate RT (54Gy/30fx) vs observation w/RT at progression.
65% in obs arm eventually got RT.
Immediate RT improved PFS (35 vs 55%) and decreased seizure rate (41 vs 25%) but did not improve OS.

(2) RTOG 9802 Ph II (J NSY 2008)
Observed pts <40yo with GTR with 5yr OS 93% and PFS 48%.
Poor prog factors: tumor 4 cm or greater, astro or mixed histo, residual disease 1 cm or more on postop MRI.
These pts must be closely watched (50% risk of progression at 5 yrs), consider adj RT.

Question 3

RT dose escalation?

Answer 3

Doesn’t help
(1) EORTC 22844 “Believers Trial” (IJROBP 1996), PRT
45Gy/25fx vs 59.4Gy/33 fx (after surgery)
RT necrosis 2.5 vs 4% and no diff in OS (60%) or PFS (50%).
Pts with dose escalation had worse QOL.

(2) RTOG 9110 (JCO 2002), PRT
50.4/28fx vs 64.8Gy/36fx (after surgery)
RT necrosis 2 vs 5%, no diff in OS (64, 72%).
92% of failures were in-field.
Stable cognitive fx 5 years out from RT

Question 4

Add PCV to RT?

Answer 4

Yes, doubles survival in high-risk pts.
RTOG 9802 Ph III (JCO 2012), PRT
Unfavorable risk (>40yo or <40 with STR)
Randomized RT alone vs RT+6c adjuvant PCV.
54Gy/30fx to T2+2 cm margin
PCV improved OS (13.3 vs 7.8 yrs)

Question 5

TMZ instead of PCV?

Answer 5

Only have level 1 data for PCV but TMZ easier to administer and better tolerated. (TBD = CODEL study)
RTOG 0424 (IJROBP 2015), single arm Ph II
RT (54Gy/30fx) with concurrent TMZ & 12c adjuvant TMZ.
High risk (3 or more risk factors): 40 or older, tumor 6 cm or bigger, tumor crossing midline, preop neuro symptoms >1, or astrocytoma).
3-yr OS 73% (compared to 54% historic control).
TMZ seems favorable but need CODEL results comparing it to PCV.