Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II CheckMate 9KD trial.

BACKGROUND: Docetaxel has immunostimulatory effects that may promote an immunoresponsive prostate tumour microenvironment, providing a rationale for combination with nivolumab (programmed death-1 inhibitor) for metastatic castration-resistant prostate cancer (mCRPC). METHODS: In the non-randomised, multicohort, global phase II CheckMate 9KD trial, 84 patients with chemotherapy-naive mCRPC, ongoing androgen deprivation therapy and ≤2 prior novel hormonal therapies (NHTs) received nivolumab 360 mg and docetaxel 75 mg/m2 every 3 weeks with prednisone 5 mg twice daily (≤10 cycles) and then nivolumab 480 mg every 4 weeks (≤2 years). The co-primary end-points were objective response rate (ORR) and prostate-specific antigen response rate (PSA50-RR; ≥50% decrease from baseline). RESULTS: The confirmed ORR (95% confidence interval [CI]) was 40.0% (25.7-55.7), and the confirmed PSA50-RR (95% CI) was 46.9% (35.7-58.3). The median (95% CI) radiographic progression-free survival (rPFS) and overall survival (OS) were 9.0 (8.0-11.6) and 18.2 (14.6-20.7) months, respectively. In subpopulations with versus without prior NHT, the ORR was 38.7% versus 42.9%, the PSA50-RR was 39.6% versus 60.7%, the median rPFS was 8.5 versus 12.0 months and the median OS was 16.2 months versus not reached. Homologous recombination deficiency status or tumour mutational burden did not appear to impact efficacy. The most common any-grade and grade 3-4 treatment-related adverse events were fatigue (39.3%) and neutropenia (16.7%), respectively. Three treatment-related deaths occurred (1 pneumonitis related to nivolumab; 2 pneumonias related to docetaxel). CONCLUSIONS: Nivolumab plus docetaxel has clinical activity in patients with chemotherapy-naïve mCRPC. Safety was consistent with the individual components. These results support further investigation in the ongoing phase III CheckMate 7DX trial. CLINICALTRIALS. GOV REGISTRATION: NCT03338790.

Recurrence rate of localized prostate cancer after radical prostatectomy according to D'amico risk classification in a tertiary referral hospital: association study.

OBJETIVO: Determinar la tasa de recurrencia del cáncer de próstata localizado después de la prostatectomía radical según la clasificación D'Amico. MÉTODOS: Estudio de cohorte retrospectivo comparativo de 5 años. Se obtuvieron datos de registros clínicos de pacientes con cáncer de próstata localizado, que se sometieron a prostatectomía radical y se evaluó la tasa de recurrencia de la enfermedad. Se analizó con pruebas estadísticas descriptivas y comparativas. Una p < 0.05 se consideró significativo. RESULTADOS: Se analizó 108 pacientes, la edad promedio 65.3 años. Acerca de la clasificación de riesgo de D'Amico, 33.33% de bajo riesgo, 55.56% riesgo intermedio y 11.11% alto riesgo. La tasa de recurrencia de APE fue 14,81%. Los pacientes de bajo riesgo tuvieron recurrencia del 13.89%, riesgo intermedio 18.33% y alto riesgo no tuvieron recurrencia. Sobre piezas quirúrgicas, el 25.93% presentaron características adversas. La escala de Gleason postoperatoria muestra un aumento de 44.44% en bajo riesgo, 26.67% en riesgo intermedio y 41.67% en alto riesgo. CONCLUSIONES: La prostatectomía radical ofrece un control adecuado del cáncer de próstata localizado. La tasa de recurrencia del APE fue menor que otros informes internacionales. Asimismo, la recurrencia bioquímica del riesgo bajo, intermedio y alto fue similar a la tendencia global. OBJECTIVE: The objective of the study was to determine the recurrence rate of localized prostate cancer after radical prostatectomy according to the D'Amico classification. METHODS: This was a observational and 5-year comparative retrospective cohort study. Data were obtained from clinical records of patients with localized prostate cancer who underwent radical prostatectomy and the recurrence rate of the disease was evaluated. It was analyzed with descriptive and comparative statistical tests, p<0.05 was considered significant. RESULTS: One hundred and eight patients were analyzed, and the average age was 65.3 years. About D'Amico's risk classification, 33.33% low risk, 55.56% intermediate risk, and 11.11% high risk. The prostate-specific antigen (PSA) recurrence rate was 14.81%. Low-risk patients had recurrence of 13.89%, intermediate risk 18.33%, and high risk had no recurrence. Regarding surgical pieces, 25.93% presented adverse characteristics. The post-operative Gleason scale shows an increase of 44.44% in low risk, 26.67% in intermediate risk, and 41.67% in high risk. CONCLUSIONS: Radical prostatectomy offers adequate control of localized prostate cancer. The PSA recurrence rate was lower than other international reports. Likewise, the biochemical recurrence of low, intermediate, and high risk was similar to the global trend.

Efficacy of the Endoscopic Combined Intrarenal Surgery for the Treatment of a Staghorn Calculus in Crossed Fused Renal Ectopia.

Background: Crossed fused renal ectopia (CFRE) is an unusual anomaly in which both kidneys lie fused on one side, with double pelvis and ureters draining into both sides of the bladder. Complex renal stones are a considerable challenge to endourologists, and when a staghorn stone is associated with abnormal anatomy, its treatment is even more difficult. Today there is no consensus about the right treatment for complex renal stones in CFRE. So, the objective of this case is to present the efficacy of the endoscopic combined intrarenal surgery (ECIRS) for the treatment of a staghorn renal stone in one patient with CFRE. Case Presentation: We described a case of a 23-year-old man with prolonged lasting and pain on the left flank associated with intermittent gross hematuria. Enhanced CT revealed a crossed fused kidney on the left side, drained by an intercommunicating pelvis and a single ureter, with a staghorn stone wholly occupying both renal units. The patient was effectively treated by one single session of ECIRS. Conclusion: The ECIRS is a good alternative to consider in patients with CFRE that have a staghorn calculus with a reasonable success rate.

Intra-coil interactions in split gradient coils in a hybrid MRI-LINAC system.

An MRI-LINAC system combines a magnetic resonance imaging (MRI) system with a medical linear accelerator (LINAC) to provide image-guided radiotherapy for targeting tumors in real-time. In an MRI-LINAC system, a set of split gradient coils is employed to produce orthogonal gradient fields for spatial signal encoding. Owing to this unconventional gradient configuration, eddy currents induced by switching gradient coils on and off may be of particular concern. It is expected that strong intra-coil interactions in the set will be present due to the constrained return paths, leading to potential degradation of the gradient field linearity and image distortion. In this study, a series of gradient coils with different track widths have been designed and analyzed to investigate the electromagnetic interactions between coils in a split gradient set. A driving current, with frequencies from 100 Hz to 10 kHz, was applied to study the inductive coupling effects with respect to conductor geometry and operating frequency. It was found that the eddy currents induced in the un-energized coils (hereby-referred to as passive coils) positively correlated with track width and frequency. The magnetic field induced by the eddy currents in the passive coils with wide tracks was several times larger than that induced by eddy currents in the cold shield of cryostat. The power loss in the passive coils increased with the track width. Therefore, intra-coil interactions should be included in the coil design and analysis process.

An analysis of the gradient-induced electric fields and current densities in human models when situated in a hybrid MRI-LINAC system.

MRI-LINAC is a new image-guided radiotherapy treatment system that combines magnetic resonance imaging (MRI) with a linear accelerator (LINAC) in a single unit. One drawback is that the pulsing of the split gradient coils of the system induces an electric field and currents in the patient which need to be predicted and evaluated for patient safety. In this novel numerical study the in situ electric fields and associated current densities were evaluated inside tissue-accurate male and female human voxel models when a number of different split-geometry gradient coils were operated. The body models were located in the MRI-LINAC system along the axial and radial directions in three different body positions. Each model had a region of interest (ROI) suitable for image-guided radiotherapy. The simulation results show that the amplitudes and distributions of the field and current density induced by different split x-gradient coils were similar with one another in the ROI of the body model, but varied outside of the region. The fields and current densities induced by a split classic coil with the surface unconnected showed the largest deviation from those given by the conventional non-split coils. Another finding indicated that the distributions of the peak current densities varied when the body position, orientation or gender changed, while the peak electric fields mainly occurred in the skin and fat tissues.

Numerical safety study of currents induced in the patient during rotations in the static field produced by a hybrid MRI-LINAC system.

MRI-LINAC is a new image-guided radiotherapy treatment system that combines magnetic resonance imaging (MRI) and a linear particle accelerator (LINAC) into a single unit. Moving (i.e., rotating or translating) the patient inside the strong magnetic field of the split MRI-LINAC magnet can potentially induce high levels of electric fields and corresponding current densities in the conducting tissues. The prediction and assessment of patient safety in terms of electromagnetic field exposure have received very little attention for a split cylindrical MRI magnet configuration, especially in the vicinity of the gap region. In this novel numerical study, based on the quasi-static finite-difference method, rotation-induced electric fields and current densities are calculated considering a split 1-T magnet and a tissue-accurate 2-mm-resolution human body model. The patient was modeled in both axial and radial orientations relative to the magnet gap in a number of treatment/imaging scenarios. It was found that rotating the patient in the radial orientation produced an order of magnitude larger field exposure in the central nervous system than when the patient was rotated in the axial orientation. Also, rotating the patient with periods lower than about Trot = 43.3 s may result in field exposures above the limits set out in the international safety guidelines. The novel results of this investigation can provide useful insights into the safe use of the MRI-LINAC technology and optimal orientations of the patient during the treatment.

Multilayer integral method for simulation of eddy currents in thin volumes of arbitrary geometry produced by MRI gradient coils.

PURPOSE: This article aims to present a fast, efficient and accurate multi-layer integral method (MIM) for the evaluation of complex spatiotemporal eddy currents in nonmagnetic and thin volumes of irregular geometries induced by arbitrary arrangements of gradient coils. METHODS: The volume of interest is divided into a number of layers, wherein the thickness of each layer is assumed to be smaller than the skin depth and where one of the linear dimensions is much smaller than the remaining two dimensions. The diffusion equation of the current density is solved both in time-harmonic and transient domain. RESULTS: The experimentally measured magnetic fields produced by the coil and the induced eddy currents as well as the corresponding time-decay constants were in close agreement with the results produced by the MIM. Relevant parameters such as power loss and force induced by the eddy currents in a split cryostat were simulated using the MIM. CONCLUSION: The proposed method is capable of accurately simulating the current diffusion process inside thin volumes, such as the magnet cryostat. The method permits the priori-calculation of optimal pre-emphasis parameters. The MIM enables unified designs of gradient coil-magnet structures for an optimal mitigation of deleterious eddy current effects.

Flanged-edge transverse gradient coil design for a hybrid LINAC-MRI system.

MRI can be combined with other systems, such as linear accelerators (LINACs) to provide image-guided therapy. However, in some configurations this requires splitting the MRI scanner to provide a central gap large enough to ensure dual access for the accelerator and the patient. This raises technical difficulties for maintaining a high gradient coil performance. In this research, a dedicated split transverse gradient coil was designed with a flange connected to the central coil end, which provided an additional surface for the current to flow. The coil was compared to existing designs, in terms of coil performance and eddy current effects. It was found that a flanged-edge coil design produced a better coil performance and more moderate eddy currents than those of the other designs. It is hoped that this study will help to inform the design of optimal gradient coils for split MRI systems with a large central gap.

Simulation and analysis of the interactions between split gradient coils and a split magnet cryostat in an MRI-PET system.

Splitting a magnetic resonance imaging (MRI) magnet into two halves can provide a central region to accommodate other modalities, such as positron emission tomography (PET). This approach, however, produces challenges in the design of the gradient coils in terms of gradient performance and fabrication. In this paper, the impact of a central gap in a split MRI system was theoretically studied by analysing the performance of split, actively-shielded transverse gradient coils. In addition, the effects of the eddy currents induced in the cryostat on power loss, mechanical vibration and magnetic field harmonics were also investigated. It was found, as expected, that the gradient performance tended to decrease as the central gap increased. Furthermore, the effects of the eddy currents were heightened as a consequence of splitting the gradient assembly into two halves. An optimal central gap size was found, such that the split gradient coils designed with this central gap size could produce an engineering solution with an acceptable trade-off between gradient performance and eddy current effects. These investigations provide useful information on the inherent trade-offs in hybrid MRI imaging systems.

Simulation and analysis of split gradient coil performance in MRI.

Split magnet systems for hybrid imaging, such as positron emission tomography-magnetic resonance imaging (PET-MRI) and Radiotherapy-MRI, require gradient coils designed with similar shapes as their corresponding main magnet. This introduces challenges in the gradient coil design of good performance and manufacturing. In this paper the effect of the gap size in shielded transverse split gradient coils and split cryostat "warm" bore over the coil efficiency, shielding efficiency, wire spacing, cryostat ohmic power loss and mechanical vibration have been simulated and studied. A "free-surface" gradient coil design method was used to design the split, actively-shielded transverse gradient coils with an axial gap. A network method was used to calculate the eddy currents induced in the split cryostat "warm" bore. The shielding efficiency and the minimum wire spacing were found to decrease when the size of the central gap is increased. The ohmic power loss and the amplitude of the radial vibrations in the split cryostat "warm" bore increases when the gap size in the gradient coil and "warm" bore is increased. It is hoped that these investigations will be useful for the development of new hybrid imaging modalities involving MRI.

Eddy current simulation in thick cylinders of finite length induced by coils of arbitrary geometry.

Eddy currents are inevitably induced when time-varying magnetic field gradients interact with the metallic structures of a magnetic resonance imaging (MRI) scanner. The secondary magnetic field produced by this induced current degrades the spatial and temporal performance of the primary field generated by the gradient coils. Although this undesired effect can be minimized by using actively and/or passively shielded gradient coils and current pre-emphasis techniques, a residual eddy current still remains in the MRI scanner structure. Accurate simulation of these eddy currents is important in the successful design of gradient coils and magnet cryostat vessels. Efficient methods for simulating eddy currents are currently restricted to cylindrical-symmetry. The approach presented in this paper divides thick conducting cylinders into thin layers (thinner than the skin depth) and expresses the current density on each as a Fourier series. The coupling between each mode of the Fourier series with every other is modeled with an inductive network method. In this way, the eddy currents induced in realistic cryostat surfaces by coils of arbitrary geometry can be simulated. The new method was validated by simulating a canonical problem and comparing the results against a commercially available software package. An accurate skin depth of 2.76 mm was calculated in 6 min with the new method. The currents induced by an actively shielded x-gradient coil were simulated assuming a finite length cylindrical cryostat consisting of three different conducting materials. Details of the temporal-spatial induced current diffusion process were simulated through all cryostat layers, which could not be efficiently simulated with any other method. With this data, all quantities that depend on the current density, such as the secondary magnetic field, are simply evaluated.