Oligoprogressive disease is a relatively new clinical concept describing progression at only a few sites of metastasis in patients with otherwise controlled widespread disease. In the era of well-tolerated targeted treatments, resistance inevitably occurs and overcoming this is a challenge. Local ablative therapy for oligoprogressive disease may allow the continuation of systemic treatments by overcoming the few sub-clones that have developed resistance. Stereotactic body radiotherapy is now frequently used in treating oligometastatic disease using ablative doses with minimally invasive techniques and acceptable toxicity. We discuss the current retrospective clinical evidence base supporting the use of local ablative therapy for oligoprogression in metastatic patients on targeted treatments within multiple tumour sites. As there is currently a lack of published prospective data available, the best management for these patients remains unclear. We discuss current trials in recruitment and the potential advancements in treating this group of patients with stereotactic radiotherapy.
Despite decades of research, the brain basis of aberrant face processing in autism spectrum disorder (ASD) remains a topic of debate. The mid‐fusiform sulcus (MFS), a minor feature of the ventral occipitotemporal cortex, provides new directions for studying face processing. The MFS closely aligns with face‐selective cortical patches and other structural and functional divisions of the fusiform gyrus; however, it has received little attention in clinical populations. We collected structural MRI data from 54 individuals with ASD and 61 age‐and‐IQ‐matched controls ages 8 to 40 years. The MFS was identified on cortical surface reconstructions via 4 trained raters and classified into known surface patterns. Mean MFS gray matter volume (GMV), cortical surface area (SA), cortical thickness (CT), and standard deviation of CT (CT SD) were extracted. Effects of diagnosis, age, and hemisphere on MFS surface presentation and morphometry were assessed via multinomial logistic regression and mixed effects general linear modeling, respectively. The MFS was reliably identified in 97% of hemispheres examined. Macroanatomical patterns and age‐related decreases in MFS GMV and CT were similar between groups. CT SD was greater in the left hemisphere in ASD. Participants' ability to interpret emotions and mental states from facial features was significantly negatively correlated with MFS CT and CT SD. Overall, the MFS is a stable feature of the fusiform gyrus in ASD and CT related measures appear to be sensitive to diagnosis and behavior. These results can inform future investigations of face processing and structure–function relationships in populations with social deficits. Lay Summary A small structural feature of the brain related to seeing faces (the mid‐fusiform sulcus; MFS) appears similar in autism spectrum disorder (ASD) and neurotypical development; however, the thickness of this structure on the left side of the brain is more variable in ASD. People who are better at judging mental states from another person's eyes tend to have thinner and less variable MFS. This feature may teach us more about face processing and how brain structure influences function in ASD.
PurposeThere are sparse data describing outcomes of bone-only oligometastatic prostate cancer in comparison with lymph node disease treated with stereotactic body radiotherapy (SBRT). The primary aim of this study was to report progression-free survival (PFS) data for patients with bone-only disease. Influence of hormone sensitivity and androgen deprivation therapy use was also assessed.MethodsThis is a single-centre retrospective cohort study. Hormone-sensitive and castrate-resistant patients with oligometastatic (≤ 3) bone-only prostate cancer treated with SBRT were included. Data were collected using electronic records. Kaplan–Meier survivor function, log rank test, as well as Cox regression were used to calculate PFS and overall survival.ResultsIn total, 51 patients with 64 bone metastases treated with SBRT were included. Nine patients were castrate resistant and 42 patient’s hormone sensitive at the time of SBRT. Median follow-up was 23 months. Median PFS was 24 months in hormone-sensitive patients and 3 months in castrate-resistant patients. No patients experienced grade 3 or 4 toxicities. There were three in-field recurrences.ConclusionsIn this study, patients with bone oligometastatic disease showed potential benefit from SBRT with a median PFS of 11 months. Hormone-sensitive patients showed the greatest benefit, with results similar to that published for oligometastatic pelvic nodal disease treated with SBRT. Prospective randomised control trials are needed to determine the survival benefit of SBRT in oligometastatic bone-only prostate cancer and to determine prognostic indicators.Electronic supplementary materialThe online version of this article (10.1007/s00345-019-02873-w) contains supplementary material, which is available to authorized users.
Urothelial carcinoma (UC) is characterized by expression of a plethora of cell surface antigens, thus offering opportunities for specific therapeutic targeting with use of antibody-drug conjugates (ADCs). ADCs are structured from two major constituents, a monoclonal antibody (mAb) against a specific target and a cytotoxic drug connected via a linker molecule. Several ADCs are developed against different UC surface markers, but the ones at most advanced stages of development include sacituzumab govitecan (IMMU-132), enfortumab vedotin (ASG-22CE/ASG-22ME), ASG-15ME for advanced UC, and oportuzumab monatox (VB4-845) for early UC. Several new targets are identified and utilized for novel or existing ADC testing. The most promising ones include human epidermal growth factor receptor 2 (HER2) and members of the fibroblast growth factor receptor axis (FGF/FGFR). Positive preclinical and early clinical results are reported in many cases, thus the next step involves further improving efficacy and reducing toxicity as well as testing combination strategies with approved agents.
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