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Magnetic resonance spectroscopy as an early indicator of response to anti-angiogenic therapy in patients with recurrent glioblastoma: RTOG 0625/ACRIN 6677.
Ratai, EM, Zhang, Z, Snyder, BS, Boxerman, JL, Safriel, Y, McKinstry, RC, Bokstein, F, Gilbert, MR, Sorensen, AG, Barboriak, DP
Neuro-oncology. 2013;(7):936-44
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Abstract
BACKGROUND The prognosis for patients with recurrent glioblastoma remains poor. The purpose of this study was to assess the potential role of MR spectroscopy as an early indicator of response to anti-angiogenic therapy. METHODS Thirteen patients with recurrent glioblastoma were enrolled in RTOG 0625/ACRIN 6677, a prospective multicenter trial in which bevacizumab was used in combination with either temozolomide or irinotecan. Patients were scanned prior to treatment and at specific timepoints during the treatment regimen. Postcontrast T1-weighted MRI was used to assess 6-month progression-free survival. Spectra from the enhancing tumor and peritumoral regions were defined on the postcontrast T1-weighted images. Changes in the concentration ratios of n-acetylaspartate/creatine (NAA/Cr), choline-containing compounds (Cho)/Cr, and NAA/Cho were quantified in comparison with pretreatment values. RESULTS NAA/Cho levels increased and Cho/Cr levels decreased within enhancing tumor at 2 weeks relative to pretreatment levels (P = .048 and P = .016, respectively), suggesting a possible antitumor effect of bevacizumab with cytotoxic chemotherapy. Nine of the 13 patients were alive and progression free at 6 months. Analysis of receiver operating characteristic curves for NAA/Cho changes in tumor at 8 weeks revealed higher levels in patients progression free at 6 months (area under the curve = 0.85), suggesting that NAA/Cho is associated with treatment response. Similar results were observed for receiver operating characteristic curve analyses against 1-year survival. In addition, decreased Cho/Cr and increased NAA/Cr and NAA/Cho in tumor periphery at 16 weeks posttreatment were associated with both 6-month progression-free survival and 1-year survival. CONCLUSION Changes in NAA and Cho by MR spectroscopy may potentially be useful as imaging biomarkers in assessing response to anti-angiogenic treatment.
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Low glucose degradation products dialysis solution modulates the levels of surrogate markers of peritoneal inflammation, integrity, and angiogenesis: preliminary report.
Kim, YL, Do, J, Park, SH, Cho, K, Park, J, Yoon, K, Cho, DK, Lee, EG, Kim, IS
Nephrology (Carlton, Vic.). 2003;:S28-32
Abstract
The presence of glucose degradation products (GDPs) in peritoneal dialysis (PD) fluids has many adverse effects, namely clinically significant abdominal pain or discomfort during infusion, inhibition of cell proliferation, impairment of inflammatory cell function, cytotoxicity, and the induction of vascular endothelial growth factor (VEGF). In a prospective, randomized, controlled trial comparing a low GDP PD solution (pH 7.0, two compartment bag: low GDP) to conventional PD solution (pH 5.5: high GDP), the overnight dialysate levels of the markers of inflammation/wound healing (hyaluronic acid (HA)), mesothelial cell mass/membrane integrity (cancer antigen 125 (CA125)), and angiogenesis (VEGF) were assessed over a 12-month period. Twenty-six newly commencing continuous ambulatory peritoneal dialysis (CAPD) patients were randomly assigned to either the Low GDP group (n = 16) or the High GDP group (n = 10). Standard peritoneal permeability analysis for membrane transport characteristics and dialysis adequacy with nutritional status (serum albumin, nPCR) were evaluated at 1, 6, and 12 months. In patients treated with high GDP solution, there was significant increase in VEGF with time (time = 1 month, 67.2 +/- 10.8; time = 6 months, 189.8 +/- 90.2; and time = 12 months, 169.3 +/- 83.1 pg/mg of protein; P < 0.05). There was no significant change of VEGF with time in the low GDP group. Significantly higher concentrations of CA125 (65.5 +/- 10.4 vs. 19.7 +/- 2.6 at 1 month, P < 0.0001; 66.6 +/- 9.8 vs. 29.7 +/- 5.0 at 6 months, P < 0.01; 68.7 +/- 10.5 vs. 30.7 +/- 10.0 U/mL at 12 months, P < 0.01) and lower concentrations of HA (114.6 +/- 18.8 vs. 254.3 +/- 69.2 at 1 month, P < 0.05; 417.5 +/- 57.2 vs. 1277.5 +/- 367.9 ng/mg of protein at 12 month, P < 0.05) were observed in the low GDP group compared with the high GDP group. In conclusion, continuous therapy with the low GDP solution modulates the levels of surrogate markers of peritoneal inflammation, integrity and angiogenesis. The results strongly suggest that the use of a low GDP solution would be beneficial to maintain the function and structural integrity of the peritoneal membrane.