Dosimetric Evaluation of PSMA PET-Delineated Dominant Intraprostatic Lesion Simultaneous Infield Boosts

Purpose: Prostate cancer is multifocal. However, there often exists a single dominant focus in the gland responsible for driving the biology of the disease. Dose escalation to the dominant lesion is a proposed strategy to increase tumor control. We applied radiobiological modeling to evaluate the dosimetric feasibility and benefit of dominant intraprostatic lesion simultaneous in-field boosts (DIL-SIB) to the gross tumor volume (GTV), defined using a novel molecular positron emission tomography (PET) probe (18F-DCFPyL) directed against prostate specific membrane antigen (PSMA). Methods and Materials: Patients with clinically localized, biopsy-proven prostate cancer underwent preoperative [ F]-DCFPyL PET/computed tomography (CT). DIL-SIB plans were generated by importing the PET/CT into the RayStation treatment planning system. GTV-PET for the DIL-SIB was defined by the highest %SUVmax (percentage of maximum standardized uptake value) that generated a biologically plausible volume. Volumetric arc–based plans incorporating prostate plus DIL-SIB treatment were generated. Tumor control probability (TCP) and normal tissue complication probability (NTCP) with fractionation schemes and boost doses specified in the FLAME (Investigate the Benefit of a Focal Lesion Ablative Microboost in Prostate Cancer; NCT01168479), PROFIT (Prostate Fractionated Irradiation Trial; NCT00304759), PACE (Prostate Advances in Comparative Evidence; NCT01584258), and hypoFLAME (Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0; NCT02853110) protocols were compared. Results: Comparative DIL-SIB plans for 6 men were generated from preoperative [ F]-DCFPyL PET/CT. Median boost GTV volume was 1.015 cm (0.42-1.83 cm ). Median minimum (D99%) DIL-SIB dose for F35 , F20 , F5 , and F5 were 97.3 Gy, 80.8 Gy, 46.5 Gy, and 51.5Gy. TCP within the GTV ranged from 84% to 88% for the standard plan and 95% to 96% for the DIL-SIB plans. Within the rest of the prostate, TCP ranged from 89% to 91% for the standard plans and 90% to 92% for the DIL-SIB plans. NTCP for the rectum NTCP was similar for the DIL-SIB plans (0.3%-2.7%) compared with standard plans (0.7%-2.6%). Overall, DIL-SIB plans yielded higher uncomplicated TCP (NTCP, 90%-94%) versus standard plans (NTCP, 83%-85%). Conclusions: PSMA PET provides a novel approach to define GTV for SIB-DIL dose escalation. Work is ongoing to validate PSMA PET-delineated GTV through correlation to coregistered postprostatectomy digitized histopathology. 18 18 3 3 BS BS BS BS

Hypofractionated stereotactic radiotherapy for intracranial meningioma: A systematic review

Background: The availability of image guidance and intensity modulation has led to the increasing use of hypofractionated stereotactic radiotherapy (hSRT) as an alternative to conventionally fractionated radiotherapy or radiosurgery for intracranial meningiomas (ICMs). As the safety and efficacy of this approach is not well characterized, we conducted a systematic review of the literature to assess the clinical outcomes of hSRT in the setting of ICMs. Methods: A systematic review of Medline and EMBASE databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies were retrospective or prospective series that examined an ICM population of ≥10 patients, delivered \u3e1 fraction of photon hSRT (≥2.5 Gy per fraction), and had a median follow-up of ≥2 years. Descriptive statistics were generated for included studies. Results: Of 1480 initial studies, 14 met eligibility criteria for inclusion, reporting on 630 patients (age range, 18-90) treated for 638 tumors. Primary radiotherapy was delivered in 37% of patients, 36% had radiation following surgery, and surgical details were unavailable for 27%. In 474 tumors assessed for radiologic response, 78% remained stable, 18% decreased in size, and 4% increased in size. Crude local control was 90%-100% as reported in 10 studies. The median late toxicity rate was 10%. The most common significant late toxicities were decreased visual acuity and new cranial neuropathy. Conclusions: With limited follow-up, the available literature suggests hSRT for ICMs has local control and toxicity profiles comparable to other radiotherapy approaches. Confirmation in larger patient cohorts with a longer duration of follow-up is required

Fear effects and group size interact to shape herbivory on coral reefs

Fear of predators (‘fear effects’) is an important determinant of foraging decisions by consumers across a range of ecosystems. Group size is one of the main behavioural mechanisms for mitigating fear effects while also providing foraging benefits to group members. Within coral reef ecosystems, fear effects have been shown to influence the feeding rates of herbivorous fishes, a key functional group that prevents macroalgal overgrowth. Yet, how fear effects and group size interact to shape macroalgal removal on coral reefs remains unclear. Here, we conducted field-based experiments using models of a common piscivorous fish, the leopard coral grouper Plectropomus leopardus and a series of macroalgal Sargassum ilicifolium assays positioned at increasing distances from the models (1, 2, 3 and 4 m) on two coral reefs in Singapore to investigate how acute fear effects shape the intensity of herbivory, and whether these effects were influenced by variation in the group size of herbivorous fishes feeding on the assays. We found acute fear effects strongly influenced the foraging behaviour of herbivorous fishes over small spatial scales. Rates of Sargassum biomass removal, feeding rates and the total number of individual feeding events were all lower near the predator model. These effects dissipated rapidly with increasing distance from the predator model and were undetectable at a distance of 4 m. We also found generally larger group sizes of herbivorous fishes further from the predator model, presumably reflecting decreased risk. Furthermore, the number of individual bites/event increased significantly with increasing group size for two common browsing fishes, Siganus virgatus and Siganus javus. Our findings highlight that acute fear effects influence the distribution and intensity of herbivory over small spatial scales. Fear effects also interacted with herbivore group size resulting in changes in the number of individual feeding events and bite rates that collectively shape the realized ecosystem function of macroalgal removal on coral reefs. Group size is an important context-dependent factor that should be considered when examining fear effects on coral reefs. A free Plain Language Summary can be found within the Supporting Information of this article

Macroalgal browsing on a heavily degraded, urbanized equatorial reef system

The removal of macroalgal biomass is critical to the health of coral reef ecosystems. Previous studies on relatively intact reefs with diverse and abundant fish communities have quantified rapid removal of macroalgae by herbivorous fishes, yet how these findings rel ate to degraded reef systems where fish diversity and abundance are markedly lower and algal biomass substantially higher, is unclear. We surveyed roving herbivorous fish communities and quantified their capacity to remove the dominant macroalga Sargassum ilicifolium on seven reefs in Singapore; a heavily degraded urbanized reef system. The diversity and abundance of herbivorous fishes was extremely low, with eight species and a mean abundance ~1.1 individuals 60 m -2 recorded across reefs. Consumption of S. ilicifolium varied with distance from Singapore's main port with consumption being 3- to 17-fold higher on reefs furthest from the port (Pulau Satumu: 4.18 g h -1 ; Kusu Island: 2.38 g h -1 ) than reefs closer to the port (0.35-0.78 g h -1 ). Video observations revealed a single species, Siganus virgatus, was almost solely responsible for removing S. ilicifolium biomass, accounting for 83% of the mass-standardized bites. Despite low herbivore diversity and intense urbanization, macroalgal removal by fishes on some Singaporean reefs was directly comparable to rates reported for other inshore Indo-Pacific reefs

Accuracy Validation of an Automated Method for Prostate Segmentation in Magnetic Resonance Imaging

Three dimensional (3D) manual segmentation of the prostate on magnetic resonance imaging (MRI) is a laborious and time-consuming task that is subject to inter-observer variability. In this study, we developed a fully automatic segmentation algorithm for T2-weighted endorectal prostate MRI and evaluated its accuracy within different regions of interest using a set of complementary error metrics. Our dataset contained 42 T2-weighted endorectal MRI from prostate cancer patients. The prostate was manually segmented by one observer on all of the images and by two other observers on a subset of 10 images. The algorithm first coarsely localizes the prostate in the image using a template matching technique. Then, it defines the prostate surface using learned shape and appearance information from a set of training images. To evaluate the algorithm, we assessed the error metric values in the context of measured inter-observer variability and compared performance to that of our previously published semi-automatic approach. The automatic algorithm needed an average execution time of ∼60 s to segment the prostate in 3D. When compared to a single-observer reference standard, the automatic algorithm has an average mean absolute distance of 2.8 mm, Dice similarity coefficient of 82%, recall of 82%, precision of 84%, and volume difference of 0.5 cm in the mid-gland. Concordant with other studies, accuracy was highest in the mid-gland and lower in the apex and base. Loss of accuracy with respect to the semi-automatic algorithm was less than the measured inter-observer variability in manual segmentation for the same task.

Fear effects and group size interact to shape herbivory on coral reefs

Fear of predators (‘fear effects’) is an important determinant of foraging decisions by consumers across a range of ecosystems. Group size is one of the main behavioural mechanisms for mitigating fear effects while also providing foraging benefits to group members. Within coral reef ecosystems, fear effects have been shown to influence the feeding rates of herbivorous fishes, a key functional group that prevents macroalgal overgrowth. Yet, how fear effects and group size interact to shape macroalgal removal on coral reefs remains unclear. Here, we conducted field-based experiments using models of a common piscivorous fish, the leopard coral grouper Plectropomus leopardus and a series of macroalgal Sargassum ilicifolium assays positioned at increasing distances from the models (1, 2, 3 and 4 m) on two coral reefs in Singapore to investigate how acute fear effects shape the intensity of herbivory, and whether these effects were influenced by variation in the group size of herbivorous fishes feeding on the assays. We found acute fear effects strongly influenced the foraging behaviour of herbivorous fishes over small spatial scales. Rates of Sargassum biomass removal, feeding rates and the total number of individual feeding events were all lower near the predator model. These effects dissipated rapidly with increasing distance from the predator model and were undetectable at a distance of 4 m. We also found generally larger group sizes of herbivorous fishes further from the predator model, presumably reflecting decreased risk. Furthermore, the number of individual bites/event increased significantly with increasing group size for two common browsing fishes, Siganus virgatus and Siganus javus. Our findings highlight that acute fear effects influence the distribution and intensity of herbivory over small spatial scales. Fear effects also interacted with herbivore group size resulting in changes in the number of individual feeding events and bite rates that collectively shape the realized ecosystem function of macroalgal removal on coral reefs. Group size is an important context-dependent factor that should be considered when examining fear effects on coral reefs

Online advertising and marketing claims by providers of proton beam therapy: Are they guideline-based?

Background: Cancer patients frequently search the Internet for treatment options, and hospital websites are seen as reliable sources of knowledge. Guidelines support the use of proton radiotherapy in specific disease sites or on clinical trials. This study aims to evaluate direct-to-consumer advertising content and claims made by proton therapy centre (PTC) websites worldwide. Methods: Operational PTC websites in English were identified through the Particle Therapy Co-Operative Group website. Data abstraction of website content was performed independently by two investigators. Eight international guidelines were consulted to determine guideline-based indications for proton radiotherapy. Univariate and multivariate logistic regression models were used to determine the characteristics of PTC websites that indicated proton radiotherapy offered greater disease control or cure rates. Results: Forty-eight PTCs with 46 English websites were identified. 60·9% of PTC websites claimed proton therapy provided improved disease control or cure. U.S. websites listed more indications than international websites (15·5 ± 5·4 vs. 10·4 ± 5·8, p = 0·004). The most common disease sites advertised were prostate (87·0%), head and neck (87·0%) and pediatrics (82·6%), all of which were indicated in least one international guideline. Several disease sites advertised were not present in any consensus guidelines, including pancreatobiliary (52·2%), breast (50·0%), and esophageal (43·5%) cancers. Multivariate analysis found increasing number of disease sites and claiming their centre was a local or regional leader in proton radiotherapy was associated with indicating proton radiotherapy offers greater disease control or cure. Conclusions: Information from PTC websites often differs from recommendations found in international consensus guidelines. As online marketing information may have significant influence on patient decision-making, alignment of such information with accepted guidelines and consensus opinion should be adopted by PTC providers