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Challenges and opportunities of using stereotactic body radiotherapy with anti-angiogenesis agents in tumor therapy.

ABSTRACT: Microvessels promote proliferation of tumor cells by delivering oxygen and nutrients, but rapid growth of tumors results in unmet demands for oxygen and nutrients, thereby creating a hypoxia microenvironment. Under hypoxic conditions, vascular endothelial cells (ECs) initiate the formation of immature and abnormal microvasculature. This results in leakage and tortuosity that facilitates tumor cell invasion, metastasis and resistance to cytotoxic treatment. Radiotherapy (RT) is a vital tumor treatment modality. Currently, more than 60% of patients with malignant tumors receive RT at certain points during their treatment. Hypoxia induced by abnormal microvessels can hamper the cytotoxic effect of ionizing radiation, particularly, stereotactic body radiotherapy (SBRT). Anti-angiogenesis (AA) agents are known to reduce and renormalize microvessels in tumors, and hence alleviate hypoxia. The combination of AA agents with SBRT may have a synergistic role in inhibiting the growth of tumors. On the contrary, large doses of irradiation may affect tumor microvessels itself. In this review, we aim to clarify the relationship between SBRT and microvessel formation in tumors. In addition, we provide a retrospective analysis of the combination therapy involving SBRT and AA agents in preclinical and clinical practice to define its role in anti-tumor treatment.

SUBMITTER: Sun X

PROVIDER: S-EPMC5842229 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Project description:Prostate cancer is the most common non-cutaneous cancer in males. There are a number of options for patients with localized early stage disease, including active surveillance for low-risk disease, surgery, brachytherapy, and external beam radiotherapy. Increasingly, external beam radiotherapy, in the form of dose-escalated and moderately hypofractionated regimens, is being utilized in prostate cancer, with randomized evidence to support their use. Stereotactic body radiotherapy, which is a form of extreme hypofractionation, delivered with high precision and conformality typically over 1 to 5 fractions, offers a more contemporary approach with several advantages including being non-invasive, cost-effective, convenient for patients, and potentially improving patient access. In fact, one study has estimated that if half of the patients currently eligible for conventional fractionated radiotherapy in the United States were treated instead with stereotactic body radiotherapy, this would result in a total cost savings of US$250 million per year. There is also a strong radiobiological rationale to support its use, with prostate cancer believed to have a low ?/? ratio and therefore being preferentially sensitive to larger fraction sizes. To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities, although multiple randomized trials are currently accruing. Yet, early results from the randomized phase III study of HYPOfractionated RadioTherapy of intermediate risk localized Prostate Cancer (HYPO-RT-PC) trial, as well as multiple single-arm phase I/II trials, indicate low rates of late adverse effects with this approach. In patients with low- to intermediate-risk disease, excellent biochemical relapse-free survival outcomes have been reported, albeit with relatively short median follow-up times. These promising early results, coupled with the enormous potential cost savings and implications for resource availability, suggest that stereotactic body radiotherapy will take center stage in the treatment of prostate cancer in the years to come.

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Challenges and opportunities of using stereotactic body radiotherapy with anti-angiogenesis agents in tumor therapy.

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