Pair-matched patient-reported quality of life and early oncological control following focal irreversible electroporation versus robot-assisted radical prostatectomy

Purpose: The design, conduct and completion of randomized trials for curative prostate cancer (PCa) treatments are challenging. To evaluate the effect of robot-assisted radical prostatectomy (RARP) versus focal irreversible electroporation (IRE) on patient-reported quality of life (QoL) and early oncological control using propensity-scored matching. Methods: Patients with T1c–cT2b significant PCa (hig

Molecular biomarkers in the context of focal therapy for prostate cancer: Recommendations of a delphi consensus from the focal therapy society

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject

Imaging modalities in focal therapy: patient selection, treatment guidance, and follow-up

Focal therapy for prostate cancer is emerging as a management option between active surveillance and radical treatments. In this article, we present two of the most important imaging modalities in focal therapy, multiparametric MRI (mpMRI) and ultrasonography. We review the recent advances within these two platforms. State-of-the-art imaging in all phases of focal therapy is essential for treatment safety. In patient selection, treatment guidance, and follow-up, different aspects of imaging are important. mpMRI is an imaging technology with high imaging resolution and contrast. This makes it an excellent technology for patient selection and treatment planning and follow-up. Ultrasound has the unique property of real-time image acquisition. This makes it an excellent technology for real-time treatment guidance. There are multiple novelties in these two platforms that have increased the accuracy considerably. Examples in ultrasound are contrast-enhanced ultrasonography, elastography, shear-wave elastography, and histoscanning. In mpMRI, these advantages consist of multiple sequences combined to one image and magnetic resonance thermometry. Standardization of multiparametric transrectal ultrasound and mpMRI is of paramount importance. For targeted treatment and follow-up, a good negative predictive value of the test is important. There is much to gain from both of these developing fields and imaging accuracy of the two platforms is comparable. Standardization in conduct and interpretation, three-dimensional reconstruction, and fusion of the two platforms can make focal therapy the standard of care for prostate cance

What is still needed to make focal therapy an accepted segment of standard therapy?

Focal therapy is gaining interest and this organ-preserving treatment is heading towards becoming an alternative for the conventional surgery and radiation. The purpose of this review is to determine what evidence is required to make focal therapy a viable option for treatment of localized prostate cancer. There is still a lack of high-level evidence for the different focal treatment modalities. The early-stage focal therapy trials are conducted including a various selection of patients and different pretreatment assessment and follow-up, resulting in incomparable data. Recent literature shows it is paramount to extend the amount of biopsies and to alter the way of taking the biopsies with the template-assisted or image-guided approach. To date, multiparametric MRI is the most effective imaging technique in selecting patients for focal therapy. Focal therapy trials are at the early stage of clinical development, with the majority still being phase I studies. To make focal therapy an accepted segment of standard therapy, it needs to proceed toward phase II and III trials. These trials should be conducted with an effective trial design, which will lead to more comparable oncological, functional and quality of life outcomes. Furthermore, it is essential to improve the localization of tumor foci in order to increase the accuracy of spatial targeting of cance

Focal vs extended ablation in localized prostate cancer with irreversible electroporation; a multi-center randomized controlled trial

\u3cp\u3eBackground: Current surgical and ablative treatment options for prostate cancer (PCa) may result in a high incidence of (temporary) incontinence, erectile dysfunction and/or bowel damage. These side effects are due to procedure related effects on adjacent structures including blood vessels, bowel, urethra and/or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective and safe in destroying PCa cells and also has the potential advantage of sparing surrounding tissue and vital structures, resulting in less impaired functional outcomes and maintaining men's quality of life. Methods/Design: In this randomized controlled trial (RCT) on IRE in localized PCa, 200 patients with organ-confined, unilateral (T1c-T2b) low- to intermediate-risk PCa (Gleason sum score 6 and 7) on transperineal template-mapping biopsies (TTMB) will be included. Patients will be randomized into focal or extended ablation of cancer foci with IRE. Oncological efficacy will be determined by multiparametric Magnetic Resonance Imaging, Contrast-Enhanced Ultrasound imaging if available, TTMP and Prostate Specific Antigen (PSA) follow-up. Patients will be evaluated up to 5 years on functional outcomes and quality of life with the use of standardized questionnaires. Discussion: There is critical need of larger, standardized RCTs evaluating long-term oncological and functional outcomes before introducing IRE and other focal therapy modalities as an accepted and safe therapeutic option for PCa. This RCT will provide important short- and long-term data and elucidates the differences between focal or extended ablation of localized, unilateral low- to intermediate-risk PCa with IRE. Trial registration: Clinicaltrials.gov database registration number NCT01835977. The Dutch Central Committee on Research Involving Human Subjects registration number NL50791.018.14.\u3c/p\u3

Image guided adaptive brachytherapy for cervical cancer: Dose contribution to involved pelvic nodes in two cancer centers

Purpose: The goal of this study was to determine the dose contributions from image guided adaptive brachytherapy (IGABT) to individual suspicious pelvic lymph nodes (pLNN) in cervical cancer patients. Data were collected in two cancer centers, University of Pittsburgh Cancer Institute (UPCI) and University Medical Center Utrecht (UMCU). Material and methods: 27 and 15 patients with node positive cervical cancer treated with HDR (high dose rate) or PDR (pulsed dose rate)-IGABT were analyzed. HDR-IGABT (UPCI) was delivered with CT/MRI compatible tandem-ring applicators with 5.0-6.0 Gy x five fractions. PDR-IGABT (UMCU) dose was delivered with Utrecht tandem-ovoid applicators with 32 x 0.6 Gy x two fractions. Pelvic lymph nodes with short axis diameter of ≥ 5 mm on pre-treatment MRI or PET-CT were contoured for all BT-plans. Dose contributions to individual pLNN expressed as D90 (dose to 90% of the volume) were calculated from dose-volume histograms as absolute and relative physical dose (% of the reference dose) for each fraction. For each node, the total dose from all fractions was calculated, expressed in EQD2 (equivalent total dose in 2 Gy fractions). Results: Fifty-seven (UPCI) and 40 (UMCU) individual pLNN were contoured. The mean D90 pLNN was 10.8% (range 5.7-25.1%) and 20.5% (range 6.8-93.3%), respectively, and therefore different in the two centers. These values translate into 2.7 Gy (1.3-6.6 Gy) EQD2 and 7.1 Gy (2.2-36.7 Gy) EQD2, respectively. Differences are caused by the location of the individual nodes in relation to the spatial dose distribution of IGABT, differences in total dose administered and radiobiology (HDR versus PDR). Conclusions: The IGABT dose contribution to individual pelvic nodes depends on patient and treatment related factors, and varies considerably

Maxwell's equations explain why irreversible electroporation will not heat up a metal stent

Irreversible Electroporation (IRE) is a promising clinical ablation therapy for the treatment of cancer, but issues with the generation of heat must be solved before safe and effective clinical results can be obtained. In the present study, we show that a metal stent will not be noticeably heated up by IRE pulses under typical clinical conditions. Derivation of this non-intuitive result required the application of Maxwell's equations to the tissue-stent configuration. Subsequently, straightforward and arguably accurate simplifications of the electric field generated by two needles in tissue surrounding a metal stent have enabled the modeling of the heat generation and the transport of heat in IRE procedures. Close to a stent that is positioned in between two needles, temperatures in a typical run of 100 s, 1 Hz pulses, may remain notably lower than without the stent. This is the explanation of the experimentally observed low temperature rim of viable tissue around the stent, whereas all tissue was non-viable without stent, found in tissue model experiments

Maxwell's equations explain why irreversible electroporation will not heat up a metal stent

Irreversible Electroporation (IRE) is a promising clinical ablation therapy for the treatment of cancer, but issues with the generation of heat must be solved before safe and effective clinical results can be obtained. In the present study, we show that a metal stent will not be noticeably heated up by IRE pulses under typical clinical conditions. Derivation of this non-intuitive result required the application of Maxwell's equations to the tissue-stent configuration. Subsequently, straightforward and arguably accurate simplifications of the electric field generated by two needles in tissue surrounding a metal stent have enabled the modeling of the heat generation and the transport of heat in IRE procedures. Close to a stent that is positioned in between two needles, temperatures in a typical run of 100 s, 1 Hz pulses, may remain notably lower than without the stent. This is the explanation of the experimentally observed low temperature rim of viable tissue around the stent, whereas all tissue was non-viable without stent, found in tissue model experiments

Irreversible Electroporation for Colorectal Liver Metastases

Image-guided tumor ablation techniques have significantly broadened the treatment possibilities for primary and secondary hepatic malignancies. A new ablation technique, irreversible electroporation (IRE), was recently added to the treatment armamentarium. As opposed to thermal ablation, cell death with IRE is primarily induced using electrical energy: electrical pulses disrupt the cellular membrane integrity, resulting in cell death while sparing the extracellular matrix of sensitive structures such as the bile ducts, blood vessels, and bowel wall. The preservation of these structures makes IRE attractive for colorectal liver metastases (CRLM) that are unsuitable for resection and thermal ablation owing to their anatomical location. This review discusses different technical and practical issues of IRE for CRLM: the indications, patient preparations, procedural steps, and different "tricks of the trade" used to improve safety and efficacy of IRE. Imaging characteristics and early efficacy results are presented. Much is still unknown about the exact mechanism of cell death and about factors playing a crucial role in the extent of cell death. At this time, IRE for CRLM should only be reserved for small tumors that are truly unsuitable for resection or thermal ablation because of abutment of the portal triad or the venous pedicle