Article Figures & Data
Figures
- FIGURE 1.
Effect of vasogenic edema in distribution of 131I-mu81C6 mAb in brain parenchyma. MRI (left) and coregistered MRI/SPECT (right) images of patients with vasogenic edema (A–C) and without vasogenic edema (E–G). Average activity ratio between 2-cm cavity margins and SCRC was 0.26 (0.11–0.38) for patients with vasogenic edema, whereas the ratio for patients without vasogenic edema was 0.05 (0.03–0.08). Thus, activity concentrations within regions of vasogenic edema were a factor of 5 higher than in those regions without vasogenic edema. D and H represent a 3-dimensional maximum-intensity-projection view of activity distribution for patients described in C and F, respectively.
- FIGURE 2.
(A) Kaplan–Meier survival plot for all patients (n = 33) and for GBM patients (n = 27). Median survival for all patients and GBM patients was 89 wk (95% CI, 61–113 wk) and 79 wk (95% CI, 52–113 wk), respectively. (B) Kaplan–Meier survival plot for GBM patients with reversible or irreversible neurotoxicity. Median survival for GBM patients who received XRT with reversible (n = 14) and irreversible neurotoxicity (n = 10) was 98 wk (95% CI, 39–126 wk) and 73 wk (95% CI, 47–116 wk), respectively.
- FIGURE 3.
Sequential registered MRI/PET images from patient 15, who received 35 Gy to 2-cm cavity margins with an initial dose rate of 0.9 Gy h−1. A uniform rim in MRI was observed 1 mo after therapy and persisted unchanged over 59 wk with minimal vasogenic edema and minimal 18F-FDG accumulation. Subsequently, grade III irreversible neurologic toxicity developed and, 118 wk after therapy, a biopsy sample was obtained, which indicated radionecrosis. However, 177 wk after therapy, new intense 18F-FDG hypermetabolic nodularities and MRI enhancements with extensive vasogenic edema were observed on registered MRI/PET images, indicative of tumor progression.
- FIGURE 4.
Scatter plot of biopsy results and neurologic toxicity among GBM tumor patients as function of average absorbed dose DCM and maximum dose rate ḊCMmax to 2-cm cavity margins. T = tumor; RN = radionecrosis; DN = delayed neurotoxicity and grade 1, 2, 3, or 4; irr = irreversible.
- FIGURE 5.
Regression analysis (95% CI) between average boost absorbed dose and median survival for newly diagnosed GBM patients receiving XRT and radiosurgery, brachytherapy, or RIT. Among the different clinical studies, including ours, an asymptotic increase in median survival as a function of average boost absorbed dose after XRT was observed. Dose estimates for Riva et al. (35) were based on an average residence time of 82 h, average cavity size of 19 cm3, and 5 courses of 131I-BC2 and BC4 mAbs for a total administered activity of 9,250 MBq. This relationship among studies confirms the relevance of limiting the absorbed dose to tumor foci to minimize normal brain tissue injury and maximize tumor control. Reoperation rates were between 40% and 60% among brachytherapy studies, whereas rate for RIT using 131I-mu81C6 mAb was 3%. RS = radiosurgery; BT = brachytherapy.
Tables
- TABLE 1
Absorbed Dose Estimates, Survival, Neurologic and Hematologic Toxicity, and Biopsy Results for 33 Patients with Newly Diagnosed Gliomas Treated with 131I-mu81C6 mAb
Patient no. Dx Sex and race Age (y) Weight (kg) KPS SCRC volume (cm3) VE Adm. activity (MBq) ḊCMMax (Gy/h) DCM (Gy) DCMXRT (Gy) DCMTotal (Gy) DWB (cGy) DBM (cGy) Survival (wk) Toxicity Biopsy NT HT 1 GBM MW 44 92 100 12.5 − 4,440 0.56 45 63 108 46 84 79 S (3) 3 2 GBM MW 47 83 100 8.6 − 4,440 0.66 52 63 115 46 81 87 S (2) 3 3 GBM MW 38 81 80 13.8 − 4,440 0.54 43 60 103 77 99 41 4 4 GBM FW 56 68 100 23.3 − 4,440 0.43 34 59 93 63 85 61 D (4, irr) 3 5 GBM MW 43 77 90 26.4 − 4,440 0.41 32 59 92 76 96 116 D (3, irr) 4 T 6 GBM FB 48 79 70 8.5 − 4,440 0.66 52 59 111 81 100 304 4 R, R, T 7 GBM FW 39 66 100 7.2 − 4,440 0.70 55 58 113 65 85 148 D (3, irr) 3 R 8 AA MW 39 81 100 13.8 − 4,400 0.52 29 60 89 62 83 291* 3 9 GBM FW 58 72 80 2.1 − 4,440 1.13 73 — 73 43 72 39 3 10 GBM FW 35 61 100 8.7 − 4,440 0.65 50 59 110 79 89 268* D (4) 4 R 11 AA MW 19 88 100 12.9 − 4,440 0.56 38 64 102 48 81 89 3 T 12 GBM MW 36 98 100 5.5 − 4,440 0.77 40 59 99 68 94 113 4 13 GBM MW 53 88 100 20.5 − 4,440 0.45 58 60 118 53 99 95 D (1) 4 T 14 GBM MW 51 77 100 2.9 − 4,440 1.01 45 61 106 77 88 123 4 R, R, T 15 GBM MW 55 84 100 3.8 − 4,440 0.90 35 75 110 40 68 172 D (3, irr) 4 R 16 GBM MW 60 75 100 2.2 − 4,440 1.12 46 65 111 37 64 35 D (3) 3 17 GBM MW 50 97 100 17.9 + 4,440 0.48 42 60 102 25 73 55 D (3, irr) 3 T 18 AA MW 38 69 100 9.4 − 4,440 0.63 25 61 86 69 78 219 D (2) 3 19 GBM MW 49 76 100 10.9 − 4,440 0.60 45 59 105 55 83 52 D (3, irr) 3 T + R 20 AO MW 68 81 100 5.5 + 4,440 0.77 50 64 114 56 83 95 D (4, irr) 3 21 AA MW 46 81 100 5.2 − 4,440 0.79 27 63 90 74 85 58 D (3) 4 T 22 GBM FW 47 71 100 8.0 − 4,440 0.67 42 60 102 56 78 77 D (4, irr) 3 R, T 23 GBM FW 59 71 100 10.0 − 4,440 0.62 45 60 105 94 101 65 D (4, irr) 4 R 24 GBM MW 60 72 100 8.1 + 4,440 0.67 34 60 94 48 71 73 D (3, irr) 3 R 25 GBM MW 38 83 100 16.3 − 4,440 0.50 34 60 94 84 101 144 3 26 GBM MW 55 105 100 16.3 + 4,440 0.50 39 60 99 51 91 126 3 27 AO FW 35 54 100 12.2 − 4,440 0.57 51 — 51 96 96 230* D (2) 3 28 GBM MW 63 70 80 1.2 + 4,440 1.35 116 — 116 44 78 24 A, S, D (3, irr) 3 29 GBM MW 53 90 100 0.5 + 4,440 1.80 113 — 113 74 97 97 A, S, D (3, irr) 4 T 30 GBM FW 65 70 100 12.1 − 4,440 0.57 77 60 137 67 102 47 D (4, irr) 4 31 GBM MW 54 108 100 4.3 + 1,369 0.26 42 60 102 14 34 50 3 32 GBM MW 52 72 100 30.5 + 4,440 0.38 65 60 125 67 112 109 4 33 GBM FW 54 76 100 13.0 + 4,440 0.56 27 60 87 52 75 27 3 ↵* Censored (alive).
Dx = diagnosis; VE = vasogenic edema; Adm. activity = administered activity; ḊCMMax = maximum initial dose rate; DCM = dose from RIT; DCMXRT = dose from XRT; DCMTotal = total dose from RIT and XRT; DWB = WB dose; DBM = bone marrow dose; NT = neurotoxicity; HT = hematologic toxicity (grade: 1, 2, 3, or 4); S = subacute; D = delayed (grade: 1, 2, 3, or 4; irr = irreversible); T = tumor; R = radionecrosis; A = acute.
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