Xstrahl In Action: Low dose treatment counteracts and enhances the anti-tumor effect
The extent of tumor oxygenation is an important factor contributing to the efficacy of radiation therapy. Several preclinical studies have shown benefit of combining radiation therapy with drugs that inhibit tumor blood vessel growth, i.e. angiostatic therapy. Recent findings show that proper scheduling of both treatment modalities allows dose reduction of angiostatic drugs without affecting therapeutic efficacy.
In their study “Low dose angiostatic treatment counteracts radiotherapy-induced tumor perfusion and enhances the anti-tumor effect.” Kleibeuker EA, Fokas E, Allen PD, Kersemans V, Griffioen AW, Beech J, Im JH, Smart SC, Castricum KC, van den Berg J, Schulkens IA, Hill SA, Harris AL, Slotman BJ, Verheul HM, Muschel RJ, Thijssen VL found that whilst low dose sunitinib (20 mg/kg/day) did not affect the growth of xenograft HT29 colon carcinoma tumors in nude mice, the combination with either single dose radiation therapy (1x 5Gy) or fractionated Radiation therapy (5x 2Gy/week, up to 3 weeks) substantially hampered tumor growth compared to either radiation therapy treatment alone.
To better understand the interaction between radiation therapy and low dose angiostatic therapy, they explored the effects of radiation therapy on tumor angiogenesis and tissue perfusion using the Xstrahl CIX3.
DCE-MRI analyses revealed that fractionated radiation therapy resulted in enhanced perfusion after two weeks of treatment. This mainly occurred in the center of the tumor and was accompanied by increased tissue viability and decreased hypoxia. These effects were accompanied by increased expression of the pro-angiogenic growth factors VEGF and PlGF. DCE-MRI and contrast enhanced ultrasonography showed that the increase in perfusion and tissue viability was counteracted by low-dose sunitinib.
Overall, the paper gives insight in the dynamics of tumor perfusion during conventional 2 Gy fractionated radiation therapy and provide a rationale to combine low dose angiostatic drugs with radiation therapy both in the palliative as well as in the curative setting.