Heart motion tracking for radiation therapy treatment planning can result in effective motion management strategies to minimize radiation-induced cardiotoxicity. However, automatic heart motion tracking is challenging due to factors that include the complex spatial relationship between the heart and its neighboring structures, dynamic changes in heart shape, and limited image contrast, resolution, and volume coverage. In this study, we developed and evaluated a deep generative shape model-driven level set method to address these challenges. The proposed heart motion tracking method makes use of a heart shape model that characterizes the statistical variations in heart shapes present in a training data set. This heart shape model was established by training a three-layered deep Boltzmann machine (DBM) in order to characterize both local and global heart shape variations. During the tracking phase, a distance regularized level-set evolution (DRLSE) method was applied to delineate the heart contour on each frame of a cine MRI image sequence. The trained shape model was embedded into the DRLSE method as a shape prior term to constrain an evolutional shape to reach the desired heart boundary. Frame-by-frame heart motion tracking was achieved by iteratively mapping the obtained heart contour for each frame to the next frame as a reliable initialization, and performing a level-set evolution. The performance of the proposed motion tracking method was demonstrated using thirty-eight coronal cine MRI image sequences.

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To describe early follow-up results of a trial of single-fraction, intra-operative radiation therapy (IORT) delivered with an electronic brachytherapy system immediately following surgical resection for treatment of early-stage breast cancer. Materials/Methods: To date, 1,028 participants have been enrolled in this open label, single-arm, prospective, non-randomized trial at 28 hospitals in the USA (27) and Portugal (1). 1,023 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by IORT to the lumpectomy cavity. A presterilized lead shield was placed on the chest wall and a balloon applicator suitable to the surgical bed was placed in the lumpectomy cavity and inflated with saline (30-75 cc). Balloon surface-to-skin distance of ! 1.0 cm was confirmed by ultrasound. Single-fraction IORT (20 Gy) was delivered at the balloon applicator surface with a mean radiation treatment time of 11.3 minutes. Following IORT, balloon was deflated and removed along with lead shielding, and surgical site was sutured. The prespecified primary outcome of this 10-year follow-up study is ipsilateral breast tumor recurrence at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Results: Median follow-up time was 1.2 years with 320, 102, and 10 participants completing 2-, 3-, and 4-year follow-up, respectively. Mean age at enrollment was 66 years (range 41-93). 246 participants had DCIS and 777 had invasive ductal carcinoma. DCIS nuclear grades were high (82), intermediate (119), or low (45) with three identified as bilateral. Invasive cancers were Grade 1 (318) including two bilateral cases, Grade 2 (340) with one bilateral case, Grade 3 (105) with two bilateral cases, or no Grade (14). Mean tumor size was 12.01 AE 10.8 mm. Cosmesis was excellent in 100% of participants at 4-year followup and excellent to good in 94% and 91% of participants at 2-and 3year follow-up, respectively. The number of reported adverse events (AEs) that were Grade 2 or higher was 169 (9%). Seroma, breast induration, erythema, breast fibrosis, and breast pain were the most frequent AEs. There were ten deaths, none of which were breast cancer related. There were six ipsilateral breast recurrences and three new contralateral breast cancers. Conclusion: Single-fraction IORT using an electronic brachytherapy system following breast conservation surgery may be a promising treatment option for select early-stage breast cancer patients. Early findings from this multicenter trial suggest that the short and convenient course of radiation therapy has low morbidity, excellent to good cosmetic results, and a low rate of high-grade adverse events and recurrences.

Transdifferentiation of epithelial cells to mesenchymal cells is called epithelial‐mesenchymal transition (EMT). EMT is a normal process during embryogenesis, where epithelial cells lose their characteristics and become more motile mesenchymal cells. Invasive and metastatic characteristics of carcinoma cells in primary tumors are mediated by EMT. Specifically, the primary tumor loses cell‐cell adhesion normally mediated by E‐cadherin and attains mesenchymal markers such as vimentin. Also, transitioning cells attain increased intercellular separation and elongated shape with pseudopodia. Studies have shown that chemotherapy and radiation therapy lead to formation of resistant cells by transdifferentiation into EMT. To study chemoresistance‐induced EMT, colon cancer (DLD‐1) cells were treated with increasing concentrations of oxaliplatin (an anti‐cancer drug used to treat metastasized colon cancer) to develop a chemo‐resistant cell line (DLD‐1 OxR). These resistant cells show properties of EMT by morphologic and cell migration measures. Previously, we showed that curcumin, a phytochemical derived from turmeric, inhibited DLD‐1 proliferation: its effect on DLD‐1 OxR suggests inhibition as well. Future studies of DLD‐1 OxR will include characterization of mesenchymal marker expression.

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