Rapid stromal remodeling by short-term VEGFR2 inhibition increases chemotherapy delivery in esophagogastric adenocarcinoma.

Anti-angiogenic agents combined with chemotherapy is an important strategy for the treatment of solid tumors. However, survival benefit is limited, urging the improvement of combination therapies. We aimed to clarify the effects of vascular endothelial growth factor receptor 2 (VEGFR2) targeting on hemodynamic function and penetration of drugs in esophagogastric adenocarcinoma (EAC). Patient-derived xenograft (PDX) models of EAC were subjected to long-term and short-term treatment with anti-VEGFR2 therapy followed by chemotherapy injection or multi-agent dynamic contrast-enhanced (DCE-) MRI and vascular casting. Long-term anti-VEGFR2-treated tumors showed a relatively lower flow and vessel density resulting in reduced chemotherapy uptake. On the contrary, short-term VEGFR2 targeting resulted in relatively higher flow, rapid vasodilation, and improved chemotherapy delivery. Assessment of the extracellular matrix (ECM) revealed that short-term anti-angiogenic treatment drastically remodels the tumor stroma by inducing nitric oxide synthesis and hyaluronan degradation, thereby dilating the vasculature and improving intratumoral chemotherapy delivery. These previously unrecognized beneficial effects could not be maintained by long-term VEGFR2 inhibition. As the identified mechanisms are targetable, they offer direct options to enhance the treatment efficacy of anti-angiogenic therapy combined with chemotherapy in EAC patients.

Pressure-based Compression Guidance of the Breast in Digital Breast Tomosynthesis Using Flexible Paddles Compared to Conventional Compression.

OBJECTIVE: We investigated the effect of introducing a pressure-based flexible paddle on compression parameters and user and patient experience of digital breast tomosynthesis (DBT) combined with patient-assisted compression or technologist compression. METHODS: After institutional review board approval, women with a DBT appointment who gave informed consent received pressure-based flexible paddle breast compression. Eight lights on the paddle were illuminated (1.9 kPa per light) as pressure was applied, aiming for an 8-13.9 kPa target range. The compression level was applied by the technologist or the participant utilizing a remote control device. The participant's and technologist's experiences were assessed by a questionnaire. Compression parameters were compared to previous examinations. Comparative statistics were performed using t-tests. RESULTS: Pressure-based compression (PBC) was judged to be similar or more comfortable compared with previous traditional exams (80%, 83/103), and 87% (90/103) of participants would recommend PBC to friends. Pressure variability decreased for craniocaudal (CC) views (-55%, P < 0.001) and mediolateral oblique (MLO) views (-34%, P < 0.0001). Subgroup analysis showed a similar glandular dose for CC views, while breast thickness was reduced (-3.74 mm, P < 0.0001). For MLO views, both glandular dose (-0.13 mGy, P < 0.0001) and breast thickness were reduced (-6.70 mm, P < 0.0001). Mean compression parameters were similar for technologist compression and patient-assisted examinations. CONCLUSION: Use of the pressure-based flexible paddle in DBT, with or without patient-assisted compression, improved participant and technologist experience and reduced compression pressure variability, mean breast thickness, and glandular dose.

Technical Note: Validation of two methods to determine contact area between breast and compression paddle in mammography.

PURPOSE: To assess the accuracy of two methods of determining the contact area between the compression paddle and the breast in mammography. An accurate method to determine the contact area is essential to accurately calculate the average compression pressure applied by the paddle. METHODS: For a set of 300 breast compressions, we measured the contact areas between breast and paddle, both capacitively using a transparent foil with indium-tin-oxide (ITO) coating attached to the paddle, and retrospectively from the obtained mammograms using image processing software (Volpara Enterprise, algorithm version 1.5.2). A gold standard was obtained from video images of the compressed breast. During each compression, the breast was illuminated from the sides in order to create a dark shadow on the video image where the breast was in contact with the compression paddle. We manually segmented the shadows captured at the time of x-ray exposure and measured their areas. RESULTS: We found a strong correlation between the manual segmentations and the capacitive measurements [r = 0.989, 95% CI (0.987, 0.992)] and between the manual segmentations and the image processing software [r = 0.978, 95% CI (0.972, 0.982)]. Bland-Altman analysis showed a bias of -0.0038 dm2 for the capacitive measurement (SD 0.0658, 95% limits of agreement [-0.1329, 0.1252]) and -0.0035 dm2 for the image processing software [SD 0.0962, 95% limits of agreement (-0.1921, 0.1850)]. CONCLUSIONS: The size of the contact area between the paddle and the breast can be determined accurately and precisely, both in real-time using the capacitive method, and retrospectively using image processing software. This result is beneficial for scientific research, data analysis and quality control systems that depend on one of these two methods for determining the average pressure on the breast during mammographic compression.