Individuals & Families

TSC Research Article Summaries: Lungs

Serum VEGF-D concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial

Author(s): Lisa R Young, MD, Hye-Seung Lee, PhD, Yoshikazu Inoue, MD, Joel Moss, MD, Lianne G Singer, MD, Prof. Charlie Strange, MD, Prof. Koh Nakata, MD, Prof. Alan F Barker, MD, Jeffrey T Chapman, MD, Prof. Mark L Brantly, MD, Prof. James M Stocks, MD, Prof. Kevin K Brown, MD, Prof. Joseph P Lynch, 3rd, MD, Hilary J Goldberg, MD, Prof. Gregory P Downey, MD, Jeffrey J Swigris, DO, Angelo M Taveira-DaSilva, MD, Prof. Jeffrey P Krischer, PhD, Prof. Bruce C Trapnell, MD, and Prof. Francis X McCormack, MD, for the MILES Trial Group
Lancet Respir Med. Aug 2013; 1(6): 445–452.
DOI: 10.1016/S2213-2600(13)70090-0

What is the topic?

A biomarker is an objectively measured and evaluated characteristic that may be used as an indicator of disease burden or response to treatment with drugs. This study examined VEFG-D, a lymphatic and blood vessel promoting growth factor related to tumor metastasis, as a biomarker for lymphangioleiomyomatosis (LAM).

What did the researchers hope to learn?

The researchers hoped to determine if the concentration of VEGF-D levels in the blood correlate to LAM disease severity or improvement in lung function with sirolimus (Rapamune) administration.

Who was studied?

Participants of the MILES trial, which consisted of women 18 years or older with a definite diagnosis of LAM (mostly sporadic LAM), were studied.

How was the study conducted?

A retrospective review of VEGF-D concentrations measured at the beginning of the trial, at 6 months and after 12 months in patients randomly assigned to receive a placebo or sirolimus was performed. Pulmonary function test results were also reviewed.

What did the researchers find?

Increased baseline VEGF-D blood concentration levels were positively associated with need for supplemental oxygen, markers of airflow obstruction and hyperventilation. Further, VEGF-D levels significantly decreased from baseline at 6 and 12 months in patients treated with sirolimus versus those treated with a placebo. Moreover, higher baseline VEGF-D levels were associated with greater improvement in forced expiratory volume, a measurement of lung function, in patients that received sirolimus treatment.

What were the limitations of the study?

This study was retrospective in nature. Also because few patients with tuberous sclerosis complex associated LAM were included in this study, the results may not extend to this population. Further, the pulmonary physiology of LAM is complicated, so it is difficult to interpret some of the results from this study, and to reconcile them with conflicting results from previous studies.

What do the results mean for you?

Elevated VEGF-D levels appear to be associated with LAM disease progression and treatment response, and these levels may be used by doctors to monitor treatment response to sirolimus. More studies are needed to fully understand the usefulness of VEGF-D levels in all LAM patients, and specifically in patients with tuberous sclerosis complex associated LAM.

This summary was written by Neera Nathan, third year medical student at the George Washington University, Washington DC and Doris Duke Clinical Research Scholar studying the dermatologic manifestations of TSC in the laboratory of Thomas Darling, MD, PhD (March  2015).