Novel autosegmentation spatial similarity metrics capture the time required to correct segmentations better than traditional metrics in a thoracic cavity segmentation workflow

Automated segmentation templates can save clinicians time compared to de novo segmentation but may still take substantial time to review and correct. It has not been thoroughly investigated which automated segmentation-corrected segmentation similarity metrics best predict clinician correction time. Bilateral thoracic cavity volumes in 329 CT scans were segmented by a UNet-inspired deep learning segmentation tool and subsequently corrected by a fourth-year medical student. Eight spatial similarity metrics were calculated between the automated and corrected segmentations and associated with correction times using Spearman\u27s rank correlation coefficients. Nine clinical variables were also associated with metrics and correction times using Spearman\u27s rank correlation coefficients or Mann-Whitney U tests. The added path length, false negative path length, and surface Dice similarity coefficient correlated better with correction time than traditional metrics, including the popular volumetric Dice similarity coefficient (respectively ρ = 0.69, ρ = 0.65, ρ =  - 0.48 versus ρ =  - 0.25; correlation p values \u3c 0.001). Clinical variables poorly represented in the autosegmentation tool\u27s training data were often associated with decreased accuracy but not necessarily with prolonged correction time. Metrics used to develop and evaluate autosegmentation tools should correlate with clinical time saved. To our knowledge, this is only the second investigation of which metrics correlate with time saved. Validation of our findings is indicated in other anatomic sites and clinical workflows. Novel spatial similarity metrics may be preferable to traditional metrics for developing and evaluating autosegmentation tools that are intended to save clinicians time

A feasibility trial of skin surface motion-gated stereotactic body radiotherapy for treatment of upper abdominal or lower thoracic targets using a novel O-ring gantry

BACKGROUND AND PURPOSE: A novel O-ring gantry can deliver stereotactic body radiation therapy (SBRT) with artificial intelligence-facilitated, CT-guided online plan adaptation. It gates mobile targets by optically monitoring skin surface motion. However, this gating solution has not been clinically validated. We conducted a trial to evaluate the feasibility of optical skin surface-guided gating for patients with mobile upper abdominal or lower thoracic malignancies treated with SBRT on this platform (NCT05030454). MATERIALS AND METHODS: Ten patients who were prescribed SBRT to a thoracic or abdominal target and were capable of breath-hold for at least 17 s enrolled. They received SBRT in five fractions with breath-hold technique and optical skin surface motion monitored-gating with a ± 2 mm tolerance. Online plan adaptation was left to the discretion of the daily treating physician. The primary endpoint was defined as successful completion of \u3e 75 % of attempted fractions. Exploratory endpoints included local control and acute grade ≥ 3 toxicity rates after three months. For adapted fractions the contouring, planning, quality assurance, and treatment delivery times were recorded. RESULTS: Forty-seven of 51 SBRT fractions (92 %) were successfully gated at breath-hold by optical skin surface motion monitoring. The tumor centroid position during breath-hold varied by a mean of approximately 2 mm. Sixty-three percent of fractions were adapted online with a median total treatment time of 78.5 min. After three months no local recurrences or acute grade ≥ 3 toxicities were observed. CONCLUSIONS: SBRT treatment to mobile targets with surface-monitored gating on a novel O-ring gantry was prospectively validated

Expression of histone deacetylase (HDAC) family members in bortezomib-refractory multiple myeloma and modulation by panobinostat

Aim: Multiple myeloma (MM) is a hematological malignancy of antibody-producing mature B cells or plasma cells. The proteasome inhibitor, bortezomib, was the first-in-class compound to be FDA approved for MM and is frequently utilized in induction therapy. However, bortezomib refractory disease is a major clinical concern, and the efficacy of the pan-histone deacetylase inhibitor (HDACi), panobinostat, in bortezomib refractory disease indicates that HDAC targeting is a viable strategy. Here, we utilized isogenic bortezomib resistant models to profile HDAC expression and define baseline and HDACi-induced expression patterns of individual HDAC family members in sensitive vs. resistant cells to better understanding the potential for targeting these enzymes.Methods: Gene expression of HDAC family members in two sets of isogenic bortezomib sensitive or resistant myeloma cell lines was examined. These cell lines were subsequently treated with HDAC inhibitors: panobinostat or vorinostat, and HDAC expression was evaluated. CRISPR/Cas9 knockdown and pharmacological inhibition of specific HDAC family members were conducted.Results: Interestingly, HDAC6 and HDAC7 were significantly upregulated and downregulated, respectively, in bortezomib-resistant cells. Panobinostat was effective at inducing cell death in these lines and modulated HDAC expression in cell lines and patient samples. Knockdown of HDAC7 inhibited cell growth while pharmacologically inhibiting HDAC6 augmented cell death by panobinostat.Conclusion: Our data revealed heterogeneous expression of individual HDACs in bortezomib sensitive vs. resistant isogenic cell lines and patient samples treated with panobinostat. Cumulatively our findings highlight distinct roles for HDAC6 and HDAC7 in regulating cell death in the context of bortezomib resistance

Imaging for Response Assessment in Radiation Oncology: Current and Emerging Techniques

Imaging in radiation oncology is essential for the evaluation of treatment response in tumors and organs at risk. This influences further treatment decisions and could possibly be used to adapt therapy. This review article focuses on the currently used imaging modalities for response assessment in radiation oncology and gives an overview of new and promising techniques within this field

The development of social behavior

Zebrafish are highly social animals that exhibit social behaviors early in their development. We review the literature on the developmental timelines and experience-dependent components of zebrafish social behavior, address the strengths and limitations of different assays used to examine the ontogeny of social behavior, and discuss how zebrafish development may be extrapolated to the developmental trajectories observed in other species. We propose a gradual development of social interaction in zebrafish, similar to humans and other animals, in which social behaviors of increasing complexity occur at distinct developmental stages