Tumor Necrosis Rate Adjusted by Tumor Volume Change Is a Better Predictor of Survival of Localized Osteosarcoma Patients

Abstract Background: Hypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small-cell lung cancer (NSCLC) patients. Vascular disrupting agents (VDAs) mainly affect blood vessels located in the central area of the tumor and lead to a rapid decrease in blood, resulting in massive apoptotic tumor cell death. Thus, we evaluate the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examine tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.Methods: A xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After the treatment, tumor tissues were stained with hematoxylin and eosin and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated by immunohistochemical staining.Results: Short-term treatment with IR alone and CKD-516+IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516+IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516+IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516+IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516+IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).Conclusions: Taken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.

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Comparison of Tumor Target Volume on Four-Dimensional Computed Tomography and 18F-FDG PET/CT in Lung Cancer

Journal of Health Science and Medical Research ◽

10.31584/jhsmr.2018.36.3.18 ◽

2018 ◽

Vol 36 (3) ◽

pp. 223

Author(s):

Keeratikarn Boonyawan ◽

Sasipilai Naivikul ◽

Putipun Puataweepong ◽

Wichana Chamroonrat ◽

Thiti Swangsilpa ◽

...

Keyword(s):

Computed Tomography ◽

Lung Cancer ◽

Volume Change ◽

Fdg Pet ◽

Gross Tumor Volume ◽

Tumor Volume ◽

Pet Ct ◽

Centroid Shift ◽

18F Fdg ◽

Fdg Pet Ct

Objective: The correlation between 18F-fluorodexyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and four-dimensional computed tomography (4DCT) based-tumor volumes is unclear. This prospective study was conducted to determine the optimal threshold of PET/CT for gross tumor volume (GTV) delineation using 4DCT as the standard reference for locally advanced lung cancer patients.Material and Methods: Ten patients with histologically proven primary lung cancer who underwent radiotherapy fromJune 2017 to March 2018 in Ramathibodi Hospital were enrolled in the study. The 4DCT simulation and 18F-FDG PET/CT simulation were performed on the same position and same date. Eight standard uptake value (SUV) thresholds of SUV 1.5.0-2.0 and 15.0-35.0% of maximum SUV were selected for contouring in order to be compared with 4DCT based tumor volumes. The comparison methods used were the mean percentage volume change, dice similarity coefficient (DSC), and 3D-centroid shift of the targets between 18F-FDG PET/CT-based gross tumor volume (GTVPET) and internal gross tumor volume (IGTV) from 4DCT.Results: The largest and smallest volume of primary tumors were 422.6 cm3 and 5.9 cm3. GTVPET contoured using SUV 1.5 (GTVPET1.5) approximated closely to IGTV in all the parameters, including volume change, DSC, and 3D-centroid shift. The best median percentage volume change, median DSC, and median centroid shift between IGTV and GTVPET1.5 were 5.55, 0.745 and 0.37, respectively.Conclusion: GTVPET contoured by 18F-FDG PET at SUV1.5 corresponded most closely to the IGTV in all parameters. Further study with a larger sample size and clinical outcome analysis is needed.

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Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma

10.21203/rs.2.19212/v4 ◽

2020 ◽

Author(s):

Min-Young Kim ◽

Jung-Young Shin ◽

Jeong-Oh Kim ◽

Kyoung-Hwa Son ◽

Yeon Sil Kim ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Mouse Model ◽

Tumor Growth ◽

Blood Vessels ◽

Tumor Necrosis ◽

Tumor Volume ◽

Lung Squamous Cell Carcinoma ◽

Ki 67 ◽

Glut 1

Abstract Background: Hypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small cell lung cancer (NSCLC) patients. CKD-516, a novel vascular disrupting agent (VDA), mainly affects blood vessels in the central area of the tumor and blocks tubulin polymerization, thereby destroying the aberrant tumor vasculature with a rapid decrease in blood, resulting in massive apoptotic tumor cell death. Therefore, we evaluated the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examined tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.Methods: A xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After treatment, tumor tissues were stained with hematoxylin and eosin, and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated using immunohistochemical staining.Results: Short-term treatment with IR alone and CKD-516+IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516+IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516+IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516+IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516+IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).Conclusions: Taken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.

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