Synergistic Effect of Anti-Angiogenic and Radiation Therapy: Quantitative Evaluation with Dynamic Contrast Enhanced MR Imaging

Abstract

PurposeWe assessed the effects of anti-angiogenic therapy (AAT) on radiation therapy (RT), evaluating the tumor growth and perfusion patterns on dynamic contrast enhanced MR (DCE-MR) images.MethodsThirteen nude mice with heterotopic xenograft cancer of human lung cancer cell line were used. To observe the interval change of the tumor size and demonstrate the time-signal intensity enhancement curve of the tumor, the mice were subdivided into four groups: control (n = 2), AAT (n = 2), RT (n = 5), and combined therapy (AART, n = 4). DCE-MR images were taken four weeks after treatment. Perfusion parameters were obtained based on the Brix model. To compare the interval size changes in the RT group with those in the AART group, repeated measures ANOVA was used. Perfusion parameters in both the RT and AART groups were compared using a Mann-Whitney U test.ResultsTumor growth was more suppressed in AART group than in the other groups. Control group showed the rapid wash-in and wash-out pattern on DCE-MR images. In contrast to RT group with delayed and prolonged enhancement, both AAT and AART groups showed the rapid wash-in and plateau pattern. The signal intensity in the plateau/time to peak enhancement (P<0.016) and the maximum enhancement ratio (P<0.016) of AART group were higher than those of RT group.ConclusionsAART showed synergistic effects in anticancer treatment. The pattern of the time-intensity curve on the DCE-MR images in each group implies that AAT might help maintain the perfusion in the cancer of AART group.

Role of vascular endothelial growth factor in radiotherapy resistance to esophageal squamous cell carcinoma

“…Liu et al (Liu et al 2020) evaluated the therapeutic effect of radiotherapy combined with apatinib (anti-angiogenesis drug) on mouse nasopharyngeal carcinoma xenograft model, and found that the tumor inhibition effect of combined therapy was stronger than that of apatinib alone or radiotherapy alone. This is similar to the research results of Koo et al (Koo et al 2016) and Gao et al (Gao et al 2015), which all indicate the synergistic effect of anti-angiogenesis therapy on radiotherapy. Moreover, compared with radiotherapy and chemotherapy, the tumor volume of patients with non-small cell lung cancer with multiple brain metastases after whole brain irradiation combined with apatinib is signi cantly reduced, and patients can get better objective remission rate and longer median progression-free survival time, but there is no signi cant difference in median overall survival time (Ren et al 2021).…”

The Tumor Vascular Endothelium as Decision Maker in Cancer Therapy

“…To improve blood perfusion and thus tumor oxygenation, again vascular normalization using anti-angiogenic-therapy was suggested ( 103 , 104 ). According to this hypothesis Koo et al recently showed that a combined radiotherapy and anti-angiogenic treatment (with the second-generation multi-targeted receptor tyrosine kinase inhibitor sunitinib malate, which inhibits PDGF and VEGF) showed synergistic effects in anti-cancer treatment using heterotopic human lung cancer xenografts ( 105 ). Herein, radiation induced extensive necrosis in the central portion of the tumors, as the immature tumor blood vessels were sensitive to radiotherapy.…”

“…When radiotherapy was then combined with anti-angiogenic treatment that inhibits the formation of immature blood vessels, the tumor perfusion was maintained and tumor necrosis was reduced. This treatment combination resulted then in a more significantly suppressed tumor growth, as vessel normalization, which achieved an efficient tumor perfusion, significantly improved tumor oxygenation that is prerequisite for the tumoricidal effects of ionizing radiation ( 105 ). In line with these findings Zhu et al could show that inhibition of hypoxia-induced angiogenesis limits the efficiency of radiotherapy ( 106 ).…”

Enhancing the management of locally advanced head and neck malignancies and cases with local/neck recurrence and metastasis through the integration of anlotinib with concurrent radiochemotherapy

“…Antiangiogenic drugs possess the ability to selectively target and inhibit the growth of neovascularization, thereby modulating blood flow and oxygenation within tumor tissues. This phenomenon results in the reoxygenation of hypoxic tumor tissues, consequently enhancing the radiosensitivity of these tissues [11,12]. Presently, both domestic and international efforts have been directed toward exploring a combined antitumor approach involving radiotherapy and antiangiogenesis therapy.…”