Vaccine responders (n = 17; 9 recurrent) | Vaccine nonresponders (n = 15; 12 recurrent) | Significance | |
---|---|---|---|
Average age | 54 ± 3 | 49 ± 4 | 0.151 * |
Karnofsky score | 81 ± 2 | 84 ± 3 | 0.210 * |
Avg time to treatment | 971 ± 462 | 288 ± 46 | 0.182 ^{†} |
TTP—recurrent pre-vac (control) | 258 ± 102 | 275 ± 55 | 0.817 ^{†} |
TTP—all post-vac | 308 ± 55 | 167 ± 22 | 0.015 ^{†} |
TTP—recurrent post-vac | 260 ± 85 | 146 ± 23 | 0.142 ^{†} |
TTS—all | 642 ± 61 | 430 ± 50 | 0.041 ^{†} |
TTS—recurrent | 599 ± 75 | 401 ± 53 | 0.067 ^{†} |
% Image-complete resection | 15/17 (88%) | 10/15 (67%) | 0.148 ^{‡} |
% Newly diagnosed | 8/17 (47%) | 3/15 (20%) | 0.064 ^{‡} |
% 1st recurrence | 7/17 (41%) | 9/15 (60%) | 0.240 ^{‡} |
% 2nd recurrence | 0/27 (0%) | 3/15 (17%) | 0.092 ^{‡} |
% ≥3rd recurrence | 2/17 (12%) | 0/15 (0%) | 0.305 ^{‡} |
% Prior chemoRx | 8/17 (47%) | 10/15 (67%) | 0.225 ^{‡} |
% Postvaccine chemoRx | 12/17 (71%) | 9/15 (60%) | 0.398 ^{‡} |
% OR | 3/17 (18%) | 1/15 (7%) | 0.350 ^{‡} |
% 1-y survival | 14/17 (82%) | 10/15 (67%) | 0.207 ^{‡} |
% 2-y survival | 7/17 (41%) | 1/15 (7%) | 0.030 ^{‡} |
% Recurrent 2-y survival | 5/9 (56%) | 1/12 (8%) | 0.029 ^{‡} |
NOTE: Vaccine responders exhibited at least 2 SDs above mean prevaccine IFN-γ production after the third vaccination. Calculations of percentage of 1-y and 2-y survival include censored values.
Abbreviations: Avg time to treatment, time from histologically confirmed diagnosis of brain tumor until time of prevaccine surgery; TTP—pre-vac, prevaccine TTP from GBM diagnosis or last recurrence before prevaccine surgery until time of prevaccine surgery; TTP—all post-vac and TTP—recurrent post-vac, immediate postvaccine TTP (the same calculation as TTP in Materials and Methods) for all GBM and all recurrent GBM patients, respectively; TTS—all and TTS—recurrent, immediate postvaccine TTS from prevaccine surgery for all GBM and for all recurrent GBM patients, respectively; % OR, proportion of patients exhibiting >50% reduction in tumor volume (objective response) by MRI after vaccination, such reductions were limited to the post-vaccine chemotherapy interval exclusively; % 2-y survival and % Recurrent 2-y survival, percentage surviving ≥730 d for all GBM patients and for all recurrent GBM patients, respectively (TTP was defined as the time from the day of surgery immediately preceding vaccination therapy to the first new scan enhancement, if verified by subsequent scans or by histology, or time from diagnosis to death due to tumor progression).
Higher response thresholds rendered TTS and TTP progressively higher in all responder relative to nonresponder groups without affecting other prognostic factors. Such thresholds could be defined by median post vaccine IFN-γ enhancement (overall TTS, 656 ± 64 and 429 ± 46 d, P = 0.024; overall TTP, 322 ± 56 and 162 ± 22 d, P = 0.005 for n = 16 responders and n = 16 nonresponders; recurrent TTS, 621 ± 81 and 402 ± 49 d, P = 0.041; recurrent TTP, 282 ± 94 and 142 ± 22 d, P = 0.065 for n = 8 responders and n = 13 nonresponders, respectively), and 2 SDs above baseline mean IFN-γ production (overall TTS, 729 ± 61 and 415 ± 41 d, P = 0.002; overall TTP, 360 ± 64 and 161 ± 20 d, P = 0.001 for n = 13 responders and n = 19 nonresponders; recurrent TTS, 736 ± 29 and 386 ± 44 d, P = 0.005; recurrent TTP, 343 ± 116 and 136 ± 19 d, P = 0.014 for n = 8 responders and n = 15 nonresponders, respectively). This trend was evident with progressively higher response thresholds up until approximately the highest quartile (i.e., n = 8 responders and n = 24 nonresponders; data not shown).
↵* One-sided t test.
↵† Log-rank test.
↵‡ Fisher's exact test.