Book I of Dostoevsky’s Demons: A Slow Start?

Book I of Dostoevsky’s Demons: A Slow Start

Influence of molecular imaging on patient selection for treatment intensification prior to salvage radiation therapy for prostate cancer: a post hoc analysis of the PROPS trial.

BACKGROUND: The impact of molecular imaging (MI) on patient management after biochemical recurrence (BCR) following radical prostatectomy has been described in many studies. However, it is not known if MI-induced management changes are appropriate. This study aimed to determine if androgen deprivation therapy (ADT) management plan is improved by MI in patients who are candidates for salvage radiation therapy. METHODS: Data were analyzed from the multicenter prospective PROPS trial evaluating PSMA/Choline PET in patients being considered for salvage radiotherapy (sRT) with BCR after prostatectomy. We compared the pre- and post-MI ADT management plans for each patient and cancer outcomes as predicted by the MSKCC nomogram. A higher percentage of predicted BCR associated with ADT treatment intensification after MI was considered as an improvement in a patient's management. RESULTS: Seventy-three patients with a median PSA of 0.38 ng/mL were included. In bivariate analysis, a positive finding on MI (local or metastatic) was associated with decision to use ADT with an odds ratio of 3.67 (95% CI, 1.25 to 10.71; p = 0.02). No factor included in the nomogram was associated with decision to use ADT. Also, MI improved selection of patients to receive ADT based on predicted BCR after sRT : the predicted nomogram 5-year biochemical-free survivals were 52.5% and 43.3%, (mean difference, 9.2%; 95% CI 0.8 to 17.6; p = 0.03) for sRT alone and ADT±sRT subgroups, while there was no statistically significant difference between subgroups before MI. CONCLUSIONS: PSMA and/or Choline PET/CT before sRT can potentially improve patient ADT management by directing clinicians towards more appropriate intensification

A Prospective, Multi-site, International Comparison of F-18 fluoro-methyl-choline, multi-parametric magnetic resonance and Ga-68 HBED-CC (PSMA-11) in men with High-Risk Features and Biochemical Failure after Radical Prostatectomy: Clinical Performance and Patient Outcomes

BACKGROUND: A significant proportion of men with rising PSA following radical prostatectomy (RP) fail prostate fossa salvage radiotherapy (SRT). This study assessed the ability of F18 fluoro-methyl-choline PET/CT(FCH), Ga-68 HBED-CC PSMA-11 PET/CT (PSMA) and pelvic multi-parametric magnetic resonance imaging (pelvic MRI) to identify men who will best benefit from SRT. METHODS: Prospective, multisite, imaging study in men with rising PSA post RP, high-risk features (PSA > 0.2ng/mL and either Gleason Score (GS) > 7 or PSA doubling time 1.0ng/mL) and negative /equivocal conventional imaging (CT and bone scan) being considered for SRT. FCH (91/91), Pelvic MRI (88/91) and PSMA (31/91) (Australia only) were performed within two weeks. Imaging was interpreted by experienced local and central reads blinded to other imaging results with consensus for discordance. Imaging results were validated using a composite reference standard. Expected management was documented pre and post- imaging, and all treatments, biopsies and PSA collected for 3 years. Treatment response to SRT was defined as > 50% PSA reduction without androgen deprivation therapy. RESULTS: Median GS, PSA at imaging and PSA doubling time were 8, 0.42(IQR 0.29-0.93) ng/mL, and 5.0 (IQR 3.3-7.6) months, respectively. Overall recurrent PCa was detected in 28% (25/88) with pelvic MRI, 32% (29/91) FCH and 42% (13/31) PSMA. This was within the prostate fossa (PF) in 21.5% (19/88), 13% (12/91) and 19% (6/31), with extra PF sites in 8% (7/88), 19% (17/91), and 32% (10/31) for MRI, FCH and PSMA (< 0.004). 94% (16/17) extra- PF sites on FCH were within the field of view of pelvic MRI. The detection rate for intrapelvic extra-PF disease was 90% (9/10) for PSMA and 31% (5/16) for MRI compared to FCH. Imaging changed expected management in 46% (42/91) FCH, and 23% (21/88) MRI. PSMA provided additive management change over FCH in a further 23% (7/31). Treatment response to SRT was higher in men with negative or PF confined vs. extra PF disease. FCH 73% (32/44) vs. 33% (3/9) (p< 0.02), pelvic MRI 70% (32/46) vs 50% (2/4), P = ns) and PSMA 88% (7/8) vs. 14% (1/7) (p<0.005). Men with negative imging (MRI, FCH +/- PSMA) had high (78%) response rates to SRT. CONCLUSION: FCH and PSMA had high detection rates for extra PF disease in men with negative/equivocal conventional imaging and BCR post RP. This impacted management and treatment responses to SRT, suggesting an important role for PET in triaging men being considered for curative SRT

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM