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Indian Pediatr 2020;57: 1188 |
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Platelet Normalized Serum Vascular Endothelial Growth Factor
Levels in Progressive Pediatric Solid Malignancies
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Atul Batra
Department of Medical Oncology, Tom Baker Cancer Center;
and University of Calgary, Calgary, Alberta, Canada.
Email:
[email protected]
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We read with interest the recently published article
by Pramanik, et al. [1]. The study reported inconsistent trends
in serum vascular endothelial growth factor (VEGF) and thrombospondin-1
(TSP-1) in 108 patients with progressive pediatric solid tumors who
received metronomic chemotherapy or placebo [1]. While higher baseline
serum VEGF levels predicted inferior overall survival, authors found
that responders with metronomic chemotherapy had significantly lower
VEGF levels at baseline compared with non-responders. Further, there was
no association of serial VEGF levels with response to metronomic
chemotherapy.
Of note, VEGF is released from the
a
granules on
platelet activation during sample collection and therefore, serum levels
are considered as an inaccurate indicator of actual measurement of
circulating VEGF [2]. Patients with disseminated cancer may have a
higher platelet count and carry even higher VEGF per platelets compared
with general population [3]. Thus, plasma is preferred over serum to
measure VEGF because collecting blood in citrate tubes avoids platelet
activation and therefore preventing the spurious high VEGF levels
released from platelets [4]. Since the authors used serum to measure
VEGF levels in pediatric patients with solid tumors in the study, the
results must be interpreted with caution [1]. However, serum VEGF levels
normalized to patient’s platelet count provides serum VEGF/platelet,
which can neutralize the effect of VEGF released from platelets while
withdrawing blood [5]. Therefore, the authors may consider analyzing the
data after calculating serum VEGF/platelet for all measurements in
individual patients, if data on platelet count is available. It will be
interesting to see if a consistent pattern is then noticed between serum
VEGF/platelet with the response to metronomic chemotherapy and survival
outcomes.
Further, the authors described the effect of baseline
serum VEGF levels with overall survival in overall population as well as
responders in patients randomized to metronomic chemotherapy arm [1].
While this finding is interesting, it is an exploratory subgroup finding
in a small number of patients, which can be interpreted as hypothesis
generating at best and therefore, should be interpreted with utmost
caution.
REFERENCES
1. Pramanik R, Tyagi A, Agarwala S, Vishnubhatla S,
Dhawan D, Bakhshi S. Evaluation of vascular endothelial growth factor
(VEGF) and Thrombospondin-1 as biomarkers of metronomic chemotherapy in
progressive pediatric solid malignancies. Indian Pediatr. 2020;57:
508-11.
2. Webb NJ, Bottomley MJ, Watson CJ, Brenchley PE.
Vascular endothelial growth factor (VEGF) is released from platelets
during blood clotting: Implications for measurement of circulating VEGF
levels in clinical disease. Clin Sci. 1998;94:395-404.
3. Salven P, Orpana A, Joensuu H. Leukocytes and
platelets of patients with cancer contain high levels of vascular
endo-thelial growth factor. Clin Cancer Res. 1999;5: 487-91.
4. Banks RE, Forbes MA, Kinsey SE, et al.
Release of the angiogenic cytokine vascular endothelial growth factor
(VEGF) from platelets: Significance for VEGF measure-ments and cancer
biology. Br J Cancer. 1998;77:956-64.
5. George ML, Eccles SA, Tutton MG, Abulafi AM, Swift
RI. Correlation of plasma and serum vascular endothelial growth factor
levels with platelet count in colorectal cancer: Clinical evidence of
platelet scavenging? Clin Cancer Res. 2000;6:3147-52.
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