Tumor vessel density linked to mRCC treatment response

By Lucy Piper, Senior medwireNews Reporter

Changes in tumor vessel density correlate with response and resistance to anti-angiogenic therapy in patients with metastatic renal cell carcinoma (mRCC), study findings suggest.

The results showed a strong relationship between reduction in tumor vessel density and tumor shrinkage following treatment, supporting the theory that tumor growth inhibition in mRCC is closely linked to the suppression of tumor vascularization by these anti-angiogenic agents, say the study researchers.

Lead researcher Andrew Reynolds (The Institute of Cancer Research, London, UK) and colleagues used tumor enhancement on arterial phase contrast-enhanced computed tomography imaging as a surrogate marker of tumor vessel density.

While there was no relationship between baseline lesion enhancement and change in lesion size in response to anti-angiogenic therapy among 23 patients with mRCC, a reduction in tumor enhancement strongly correlated with reduction in lesion size (r=0.654).

Based on these two factors, the researchers classified lesions into four response subgroups. Lesions in response subgroup 1 showed a good vascular response, with a reduction in lesion enhancement of at least 50%, together with significant tumor shrinkage of at least 30%.

In response subgroup 2, the vascular response was good, with lesion enhancement reduced by 50% or more, but tumor shrinkage was limited, at between a 30% reduction and a 20% increase in diameter, reflecting disease stabilization.

“Adaptation of tumor cells to loss of a vasculature may be an important mechanism of intrinsic resistance to anti-angiogenic therapy and may explain, at least in part, why good vascular response does not always result in significant tumor shrinkage,” the team writes in the British Journal of Cancer.

For response subgroups 3 and 4, the vascular response was weaker (<50% reduction in lesion enhancement) and in terms of tumor size, there was disease stabilization (<30% reduction in size, and <20% increase in size) or disease progression (≥20% increase in size), respectively.

This suggests the presence of tumor vessels that are not affected by treatment as another important source of intrinsic resistance to anti-angiogenics, say Reynolds et al.

Lesion responses not only differed among patients but also among lesions in the same patient, the researchers report, which “poses challenges in terms of optimal patient management and continuation of therapy, and may herald early treatment failure.”

The findings suggest that more sustained inhibition of angiogenesis may help circumvent acquired resistance, say Reynolds and colleagues, who note that re-establishment of vasculature was more pronounced in lesions that showed a partial response than in those showing stable disease.

“If the biological mechanism mediating acquired resistance in [partial response] lesions is different to that of [stable disease] lesions, then this may influence the type of therapeutic approach necessary to combat acquired resistance in these different scenarios,” they suggest.

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