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Thyroglobulin levels following remnant ablation do not predict I-131 scan results
Otolaryngology– Head and Neck Surgery Volume 129 Number 2
Thyroglobulin Levels following Remnant Ablation Do Not Predict I-131 Scan Results Keith Michael Pritchyk MD (presenter); Fredrick Yeganeh MD; Kenneth D Burman MD; Bruce J Davidson MD; Matthew D Ringel MD Arlington VA; Washington DC; Washington DC; Washington DC; Washington DC
Problem: Improvements in the sensitivity of serum thyroglobulin (Tg) measurement have resulted in increasing reliance on this test in monitoring patients for thyroid cancer recurrence. To achieve adequate sensitivity for disease detection, TSH stimulation has traditionally been required for Tg monitoring. However, it has been reported that patients who demonstrate undetectable serum Tg levels on L-thyroxine following ablative radioiodine are rarely retreated and might not require subsequent I-131 scanning. Methods: 104 consecutive patients with differentiated thyroid carcinoma who had undergone total thyroidectomy and ablative radioiodine therapy were analyzed. All patients had post-ablative Tg measurements while on L-thyroxine therapy and one-year follow-up thyroxine withdrawal whole-body radioiodine scans. The serum Tg measurements were performed using an IRMA with a sensitivity of 0.5 ng/mL. Any serum Tg greater than 1.0 ng/mL was considered to be positive either during L-T4 suppression or after thyroxine withdrawal. Results: 39% of 74 patients with undetectable serum Tg while on T4 therapy had evidence of residual thyroid tissue on subsequent withdrawal whole-body scan or Tg compared to 80% of the 30 patients with a detectable Tg on suppressive therapy (RR 6.21 [1.61-23.91]). Conclusion: The first thyroglobulin level during L-T4 suppression predicts the presence of residual tissue, but a substantial number of patients with undetectable Tg levels also had residual or recurrent thyroid tissue. Significance: The initial Tg level on L-T4 suppression following remnant ablation does not appear to be an appropriate determinant for less intensive surveillance the following year. Support: None reported. R041 Effects of ACE Inhibitor, Perindopril, on Angiogenesis in HNSCC Cell Line Ryuji Yasumatsu MD (presenter); Torahiko Nakashima MD PhD; Muneyuki Masuda; Kuratomi Yuichiro MD; Tomoya Yamamoto MD; Komiyama Sohtaro MD Fukuoka Japan; Fukuoka Japan; Fukuoka Japan; Fukuoka-shi Japan; Fukuoka City Japan; Fukuoka City Japan
Problem: Angiotensin I– converting enzyme (ACE) inhibitor is widely used in the treatment of several cardiovascular diseases and hypertensive diseases. Recently, it has been
reported that ACE inhibitors have anti-cancer activity. Mechanistic studies indicate that ACE inhibitors have various anticancer effects, such as inhibition of angiogenesis and extracellular matrix degradation. In particular, the ACE inhibitor Perindopril significantly inhibits tumor growth and angiogenesis in hepatocellular carcinoma cells along with suppression of VEGF level. However, to the best of our knowledge, there are no previous studies on this subject related to head and neck squamous cell carcinoma (HNSCC). Methods: In the present study, we investigated the effect of Perindopril on VEGF expression, angiogenesis, and tumor development of HNSCC by in vitro and in vivo growth studies. Results: In the cell proliferation assays, there was no significant difference in the cell number among 1 M Perindopril-treated group and the control group in vitro. However, 1 M Perindopril showed a significant reduction in mRNA expression of VEGF in comparison to the control group. In the reporter assays, treatment with 1 M Perindopril inhibited induction in the activity of the VEGF promoter. Perindopril had a significantly inhibitory effect on the growth of SCCVIIs (mouse SCC cell line) in vivo. Conclusion: Perindopril had no direct cytotoxicity against tumor cells. However, Perindopril inhibited tumor growth due to suppression of VEGF-induced angiogenesis in vivo. Significance: The ACE inhibitor Perindopril has a potential as a useful anti-tumor agent clinically. Support: None reported. R042 Trifunctional Bispecific Antibodies Induce Tumor Cell Killing of HNSCC Silke Gronau (presenter); Michael Schmitt MD; Bernard Thess; Herbert Riechelmann MD Ulm Germany; Ulm Germany; Ulm Germany; Ulm Germany
Problem: The trifunctional bispecific antibody Removab bridges and activates CD3 positive T cells to EpCAM on carcinoma cells and simultaneously binds to an accessory immune cell–inducing tumor cell lysis. But these antitumor antibodies may cause severe adverse effects due to systemic cytokine release if given intravenously. This should not occur if allogenic peripheral mononuclear cells (PBMC) are first opsonized with the antibody ex vivo. After activation of the PBMC with Removab, the PBMC are retransfused and should induce a tumor cell lysis. Removab-induced tumor cytotoxicity and the antitumor effect of PBMC, activated with Removab, should be assessed in an autologous human ex vivo system on the chorioallantois membrane of chicken embryos. Methods: Tumor cells and autologous PBMC were obtained from 30 patients with head and neck squamous cell carcinomas (HNSCC). 4 ⫻ 106 PBMC were coincubated with 50 ng Removab for 2 hours. Uncoupled antibodies and toxic cytokines, released upon antibody binding, were then
POSTERS
R040
Research Posters P167
Thyroglobulin Levels following Remnant Ablation Do Not Predict I-131 Scan Results Keith Michael Pritchyk MD (presenter); Fredrick Yeganeh MD; Kenneth D Burman MD; Bruce J Davidson MD; Matthew D Ringel MD Arlington VA; Washington DC; Washington DC; Washington DC; Washington DC
Problem: Improvements in the sensitivity of serum thyroglobulin (Tg) measurement have resulted in increasing reliance on this test in monitoring patients for thyroid cancer recurrence. To achieve adequate sensitivity for disease detection, TSH stimulation has traditionally been required for Tg monitoring. However, it has been reported that patients who demonstrate undetectable serum Tg levels on L-thyroxine following ablative radioiodine are rarely retreated and might not require subsequent I-131 scanning. Methods: 104 consecutive patients with differentiated thyroid carcinoma who had undergone total thyroidectomy and ablative radioiodine therapy were analyzed. All patients had post-ablative Tg measurements while on L-thyroxine therapy and one-year follow-up thyroxine withdrawal whole-body radioiodine scans. The serum Tg measurements were performed using an IRMA with a sensitivity of 0.5 ng/mL. Any serum Tg greater than 1.0 ng/mL was considered to be positive either during L-T4 suppression or after thyroxine withdrawal. Results: 39% of 74 patients with undetectable serum Tg while on T4 therapy had evidence of residual thyroid tissue on subsequent withdrawal whole-body scan or Tg compared to 80% of the 30 patients with a detectable Tg on suppressive therapy (RR 6.21 [1.61-23.91]). Conclusion: The first thyroglobulin level during L-T4 suppression predicts the presence of residual tissue, but a substantial number of patients with undetectable Tg levels also had residual or recurrent thyroid tissue. Significance: The initial Tg level on L-T4 suppression following remnant ablation does not appear to be an appropriate determinant for less intensive surveillance the following year. Support: None reported. R041 Effects of ACE Inhibitor, Perindopril, on Angiogenesis in HNSCC Cell Line Ryuji Yasumatsu MD (presenter); Torahiko Nakashima MD PhD; Muneyuki Masuda; Kuratomi Yuichiro MD; Tomoya Yamamoto MD; Komiyama Sohtaro MD Fukuoka Japan; Fukuoka Japan; Fukuoka Japan; Fukuoka-shi Japan; Fukuoka City Japan; Fukuoka City Japan
Problem: Angiotensin I– converting enzyme (ACE) inhibitor is widely used in the treatment of several cardiovascular diseases and hypertensive diseases. Recently, it has been
reported that ACE inhibitors have anti-cancer activity. Mechanistic studies indicate that ACE inhibitors have various anticancer effects, such as inhibition of angiogenesis and extracellular matrix degradation. In particular, the ACE inhibitor Perindopril significantly inhibits tumor growth and angiogenesis in hepatocellular carcinoma cells along with suppression of VEGF level. However, to the best of our knowledge, there are no previous studies on this subject related to head and neck squamous cell carcinoma (HNSCC). Methods: In the present study, we investigated the effect of Perindopril on VEGF expression, angiogenesis, and tumor development of HNSCC by in vitro and in vivo growth studies. Results: In the cell proliferation assays, there was no significant difference in the cell number among 1 M Perindopril-treated group and the control group in vitro. However, 1 M Perindopril showed a significant reduction in mRNA expression of VEGF in comparison to the control group. In the reporter assays, treatment with 1 M Perindopril inhibited induction in the activity of the VEGF promoter. Perindopril had a significantly inhibitory effect on the growth of SCCVIIs (mouse SCC cell line) in vivo. Conclusion: Perindopril had no direct cytotoxicity against tumor cells. However, Perindopril inhibited tumor growth due to suppression of VEGF-induced angiogenesis in vivo. Significance: The ACE inhibitor Perindopril has a potential as a useful anti-tumor agent clinically. Support: None reported. R042 Trifunctional Bispecific Antibodies Induce Tumor Cell Killing of HNSCC Silke Gronau (presenter); Michael Schmitt MD; Bernard Thess; Herbert Riechelmann MD Ulm Germany; Ulm Germany; Ulm Germany; Ulm Germany
Problem: The trifunctional bispecific antibody Removab bridges and activates CD3 positive T cells to EpCAM on carcinoma cells and simultaneously binds to an accessory immune cell–inducing tumor cell lysis. But these antitumor antibodies may cause severe adverse effects due to systemic cytokine release if given intravenously. This should not occur if allogenic peripheral mononuclear cells (PBMC) are first opsonized with the antibody ex vivo. After activation of the PBMC with Removab, the PBMC are retransfused and should induce a tumor cell lysis. Removab-induced tumor cytotoxicity and the antitumor effect of PBMC, activated with Removab, should be assessed in an autologous human ex vivo system on the chorioallantois membrane of chicken embryos. Methods: Tumor cells and autologous PBMC were obtained from 30 patients with head and neck squamous cell carcinomas (HNSCC). 4 ⫻ 106 PBMC were coincubated with 50 ng Removab for 2 hours. Uncoupled antibodies and toxic cytokines, released upon antibody binding, were then
POSTERS
R040
Research Posters P167