Oral Scientific Abstract 36; Table

0 Gy 0 Gy 30 Gy 30 Gy 60 Gy 60 Gy

T LN T LN T LN

Absolute ADC value change in m/s2

ADC (SD) 1300 (423) 1210 (310) 1544 (388) 1497 (488) 1569 (469) 1518 (301)ADC increase and volume decrease relative to baseline images in %ADC (SD) 24 (14) 22 (5) 20 (9) 27 (8)Volume VIBE (SD) 37 (8) 21 (23) 60 (21) 45 (29)Volume CT (SD) 41 (7) 14 (15) 61 (6) 47 (14)

Oral Scientific Abstract 37; Table

Pts with RT-AE, n (%)P+TMZ+RTN Z 447

BEV+TMZ+RTN Z 464

RT skin injury 41 (9.2) 39 (8.4)RT alopecia - 2 (0.4)RT injury - 2 (0.4)RT-associated pain - 1 (0.2)RT necrosis 1 (0.2) -Total number of pts with RT-AE, n 42 44

International Journal of Radiation Oncology � Biology � PhysicsS16

registration, tumor (T) and affected lymph nodes (LNs) were contoured on

CT, post gadolinium T1-weighted ultrafast gradient echo (VIBE), and

ADC images for the purpose of comparing volumetric tumor regression

and change of ADC signal with tumor response.

Results: Mean absolute ADC values and relative ADC and volume

changes during radiation therapy are shown in the Table. At the end of

therapy, four of five patients had partial response, and one had stable

disease according to RECIST 1.1. There was no significant difference in

ADC increase and VIBE or CT volume reduction between responding and

non-responding patients or between tumor cell types in this small group.

Conclusions: The preliminary results of this study show ADC signal

increases early during therapy. While volume reduction continues during

therapy, ADC signal does not significantly change between the 30 Gy and

60 Gy time points. Further research needs to be undertaken to investigate

the predictive value of ADC signal change for tumor response, local

control, and as a basis for adaptive radiation therapy planning.

Author Disclosure: E. Weiss: E. Research Grant; Varian Medical Systems,

Philips Medical Systems. N. Royalty; UpToDate. J.C. Ford: None. K.

Olsen: None. G.D. Hugo: None.

37The Addition of Bevacizumab (BEV) to Temozolomide (TMZ) andRadiation Therapy (RT) in Newly Diagnosed Glioblastoma (GBM)Improves Progression-Free Survival (PFS) Without Adding to RTToxicityF. Saran,1 R. Henriksson,2 W. Mason,3 W. Wick,4 R. Nishikawa,5

T. Cloughesy,6 M. Hilton,7 Y. Kerloeguen,8 and O.L. Chinot9; 1The Royal

Marsden NHS Foundation Trust, Surrey, United Kingdom, 2Regional

Cancer Center Stockholm and Umea University, Stockholm/Umea,

Sweden, 3Princess Margaret Hospital, Toronto, ON, Canada, 4University

Medical Center, Heidelberg, Germany, 5Saitama Medical University,

Saitama, Japan, 6University of California, Los Angeles, CA, 7F. Hoffmann-

La Roche Ltd, Basel, Switzerland, 8F. Hoffmann-La Roche, Basel,

Switzerland, 9Aix-Marseille University, AP-HM, Service de Neuro-

Oncologie, CHU Timone, Marseille, France

Purpose/Objective(s): In AVAglio, the first phase III, randomized,

double-blind, placebo [P]-controlled trial of BEV+TMZ+RT for newly

diagnosed GBM, BEV significantly prolonged PFS and positively

impacted patient outcomes, including maintained health-related quality of

life (HRQOL) and functional independence, and reduced corticosteroid

requirements. The current analysis examined RT-related safety; we also

report the rates of pseudoprogression (PsPD).

Materials/Methods: Randomized patients (ITT: n Z 921) �18 yrs

received P or BEV (10 mg/kg, q2w) with 6 wks of TMZ (75 mg/m2/d) +

RT (2 Gy, 5d/wk), followed by 28 treatment-free days, then 6 TMZ

maintenance cycles (150-200 mg/m2/d, 5d q4w) with P or BEV (10 mg/kg,

q2w), then single-agent P or BEV (15 mg/kg, q3w) until PD/unacceptable

toxicity. Co-primary endpoints: investigator-assessed PFS, overall survival.

Secondary endpoints included safety, HRQOL.

Results: Baseline characteristics were well balanced between BEV (n Z458) and P (nZ 463). BEV significantly prolonged PFS (HR 0.64, 95% CI

0.55-0.74, p < 0.0001; median 10.6 vs 6.2 mo). Cumulative RT dose was

similar in both arms (median [range] BEV vs P: 60.0 [2.0-66.0] vs 60.0

[0.4-64.0] Gy), as was RT duration (6.1 [0.1-11.1] vs 6.1 [0.3-7.4] wks)

and proportion of patients completing �90% planned RT dose (96.3% vs

95.5%). Of patients randomized to P, 12 received �1 dose of BEV and

were included in the BEV safety population. There was no evidence of

exacerbation of AEs commonly associated with RT (RT-AE), and no major

imbalance between arms in any typical RT-AEs (Table). Wound healing

complications were more frequently observed in patients on BEV

compared with P (3.7% vs 2.2%), but the majority resolved with treatment.

RT modification or discontinuation due to AEs occurred in 4.3% and 6.0%

of patients in the BEV and P arms, respectively. Specific operational

guidance designed to prevent erroneous determination of PsPD likely

resulted in the lower rates of PsPD observed in both treatment arms

compared to those reported previously. However, the rate of confirmed

PsPD at the end of the second maintenance cycle was notably lower with

BEV compared with P (2.2% vs 9.3%).

Conclusions: The addition of BEV to TMZ+RT achieved a significant PFS

benefit without adding to the expected low toxicity profile of the combined

modality treatment. Furthermore, the rate of PsPD was substantially

reduced after treatment with BEV+TMZ+RT compared with P+TMZ+RT.

Author Disclosure: F. Saran: G. Consultant; F. Hoffmann-La Roche. H.

Travel Expenses; F. Hoffmann-La Roche. R. Henriksson: G. Consultant; F.

Hoffmann-La-Roche. W. Mason: G. Consultant; F. Hoffmann-La Roche.

W. Wick: E. Research Grant; Boehringer-Ingelheim, Alogenix, MSD. F.

Honoraria; MSD, F. Hoffmann-La Roche. G. Consultant; F. Hoffmann-La

Roche, Eli Lilly. R. Nishikawa: G. Consultant; F. Hoffmann-La Roche. T.

Cloughesy: G. Consultant; F. Hoffmann-La Roche, Genentech, Merck,

Merck Serono, Celgene, Tocagen, Apogenics, Newgen. M. Hilton: D.

Employment Other; F. Hoffmann-La Roche. H. Travel Expenses; F.

Hoffmann-La Roche. Y. Kerloeguen: A. Employee; F. Hoffmann-La

Roche. O.L. Chinot: E. Research Grant; F. Hoffmann-La Roche, Schering-

Plough. F. Honoraria; F. Hoffmann-La Roche, AstraZeneca, MSD. G.

Consultant; F. Hoffmann-La Roche.

38Phase 2 Trial of Temozolomide Plus Bevacizumab, Lithium, andRadiation Treatment for Newly Diagnosed High-Grade Gliomas:Interim AnalysisM. Tam, M. Gruber, D. Gruber, J. Golfinos, E. Parker, D. Zagzag,

and A. Narayana; New York University School of Medicine, New York, NY

Purpose/Objective(s): Anti-angiogenic therapy produces impressive

radiological and clinical responses in high grade gliomas that translate into

improved progression-free survival. However, increased invasiveness is the

dominant escape mechanism following angiogenic blockade in high grade