Preclinical Tumor Growth Delay Is More Reliably Derived From Imaging-Based Volume Measurements Than Manual Caliper Measurements
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Purpose: Tumor growth delay is frequently used in preclinical experiments evaluating oncologic interventions. While treatment response in humans is based on imaging criteria, manual caliper measurement of subcutaneous tumors is standard in animal studies. In a murine tumor model treated with immunotherapy (ImT) and radiotherapy (RT), we tested the reliability of caliper measurements through comparison of normalized tumor growth delay (NTGD) rates derived from hand- and image-based volumetrics.
Methods: Thirty syngeneic mice were inoculated with 4T1 breast cancer cells to the inguinal mammary fatpad and right axilla. One RT fraction of 8 Gy was delivered to the inguinal tumor on day 11 post-implant and intraperitoneal ImT injections were administered on days 11, 12, and 14. Each mouse underwent 3 MRI scans (days 10, 17 and 20). Caliper measurements were also performed by two independent observers, averaged, and used to estimate ellipsoid tumor volumes. MRIs were used for segmentation and volume estimation. Later tumor volumes (days 17 & 20) were normalized against baseline pre-treatment tumor volume (day 10). Normalized tumor growth delay (NTGD) rates derived from hand- and image-based volumetrics were compared to assess the reliability of calipers vs. MRI.
Results: Caliper volumes between the two observers correlated at 0.799 (Pearson, p < 0.001). The averaged caliper volumes correlated with MRI volumes at 0.897 (Pearson, p < 0.001). Absolute volume differences between caliper and MRI volumes increased with tumor growth. NTGD derived rates showed no correlation, with only 15% of NTGD caliper rates being within 10% of the MRI rates.
Conclusion: NTGD rate based on caliper volumes is a standard measure of treatment response in preclinical studies. In this experiment, caliper-derived NTGD rates did not correlate with MRI ground truth. These findings suggests that tumor volumetrics derived from stored and verifiable imaging should become standard in preclinical assessment of oncologic interventions.
Keywords
Taxonomy
IM- MRI : General (Most aspects)
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