The use of particle accelerators in radiotherapy has significantly changed the therapeutic outcomes for many types of solid tumours. In particular, protons are well known for sparing normal tissues ...and increasing the overall therapeutic index. Recent studies show that normal tissue sparing can be further enhanced through proton delivery at 100 Gy/s and above, in the so-called FLASH regime. This has generated very significant interest in assessing the biological effects of proton pulses delivered at very high dose rates. Laser-accelerated proton beams have unique temporal emission properties, which can be exploited to deliver Gy level doses in single or multiple pulses at dose rates exceeding by many orders of magnitude those currently used in FLASH approaches. An extensive investigation of the radiobiology of laser-driven protons is therefore not only necessary for future clinical application, but also offers the opportunity of accessing yet untested regimes of radiobiology. This paper provides an updated review of the recent progress achieved in ultra-high dose rate radiobiology experiments employing laser-driven protons, including a brief discussion of the relevant methodology and dosimetry approaches.
Charged particle beams driven to ultra-high dose rates (UHDRs) have been shown to offer potential benefits for future clinical applications, particularly in the reduction of normal-tissue toxicity. ...Studies of the so-called FLASH effect have shown promise, generating huge interest in high dose rate radiation studies. With laser-driven proton beams, where the duration of the proton burst delivered to a sample can be as short as hundreds of picoseconds, the instantaneous dose rates are several orders of magnitude higher than those used for conventional radiotherapy. The dosimetry of these beam modalities is not trivial, with conventional active detectors, such as ionisation chambers, experiencing saturation effects making them unusable at the extremely high dose rates. Calorimeters, measuring the radiation-induced temperature rise in an absorber, offer an ideal candidate for the dosimetry of UHDR beams. However, their application in the measurement of laser-driven UHDR beams has so far not been trialled, and their effective suitability to work with the quasi-instantaneous and inhomogeneous dose deposition patterns and the harsh environment of a laser-plasma experiment has not been tested. The measurement of the absorbed dose of laser-driven proton beams was conducted in a first-of-its-kind investigation, employing the VULCAN-PW laser system of the Central Laser Facility (CLF) at the Rutherford Appleton Laboratory (RAL), using a small-body portable graphite calorimeter (SPGC) developed at the National Physical Laboratory (NPL) and radiochromic films. A small number of shots were recorded, with the corresponding absorbed dose measurements resulting from the induced temperature rise. The effect of the electromagnetic pulse (EMP) generated during laser–target interaction was assessed on the system, showing no significant effects on the derived signal-to-noise ratio. These proof-of-principle tests highlight the ability of calorimetry techniques to measure the absorbed dose for laser-driven proton beams.
•High-grade non-muscle invasive bladder cancer treated with transurethral resection of bladder tumor (TURB) plus bacillus of Calmette-Guerin (BCG).•Up to 40% of patients have recurrence/progression ...within 2 years despite BCG.•Before starting BCG therapy, a re-TURB is performed within 2 to 6 weeks.•Worse prognosis: multifocality, lymphovascular invasion, and high-grade on re-TURB.•BCG unresponsive patients report worse oncological outcomes.
Seventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis.
Patients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients.
A total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05–1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22–2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02–1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P < 0.0001) and at 10 years (44.2% vs. 74.4%, P < 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P < 0.0001) and at 10 years (72.3% vs. 87.2%, P < 0.0001).
Multifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes.
We aimed to review the current state‐of‐the‐art imaging methods used for primary and secondary staging of prostate cancer, mainly focusing on multiparametric magnetic resonance imaging and ...positron‐emission tomography/computed tomography with new radiotracers. An expert panel of urologists, radiologists and nuclear medicine physicians with wide experience in prostate cancer led a PubMed/MEDLINE search for prospective, retrospective original research, systematic review, meta‐analyses and clinical guidelines for local and systemic staging of the primary tumor and recurrence disease after treatment. Despite magnetic resonance imaging having low sensitivity for microscopic extracapsular extension, it is now a mainstay of prostate cancer diagnosis and local staging, and is becoming a crucial tool in treatment planning. Cross‐sectional imaging for nodal staging, such as computed tomography and magnetic resonance imaging, is clinically useless even in high‐risk patients, but is still suggested by current clinical guidelines. Positron‐emission tomography/computed tomography with newer tracers has some advantage over conventional images, but is not cost‐effective. Bone scan and computed tomography are often useless in early biochemical relapse, when salvage treatments are potentially curative. New imaging modalities, such as prostate‐specific membrane antigen positron‐emission tomography/computed tomography and whole‐body magnetic resonance imaging, are showing promising results for early local and systemic detection. Newer imaging techniques, such as multiparametric magnetic resonance imaging, whole‐body magnetic resonance imaging and positron‐emission tomography/computed tomography with prostate‐specific membrane antigen, have the potential to fill the historical limitations of conventional imaging methods in some clinical situations of primary and secondary staging of prostate cancer.
Developing compact ion accelerators using intense lasers is a very active area of research, motivated by a strong applicative potential in science, industry and healthcare. However, proposed ...applications in medical therapy, as well as in nuclear and particle physics demand a strict control of ion energy, as well as of the angular and spectral distribution of ion beam, beyond the intrinsic limitations of the several acceleration mechanisms explored so far. Here we report on the production of highly collimated (Formula: see text half angle divergence), high-charge (10s of pC) and quasi-monoenergetic proton beams up to Formula: see text 50 MeV, using a recently developed method based on helical coil targetry. In this concept, ions accelerated from a laser-irradiated foil are post-accelerated and conditioned in a helical structure positioned at the rear of the foil. The pencil beam of protons was produced by guided post-acceleration at a rate of Formula: see text 2 GeV/m, without sacrificing the excellent beam emittance of the laser-driven proton beams. 3D particle tracing simulations indicate the possibility of sustaining high acceleration gradients over extended helical coil lengths, thus maximising the gain from such miniature accelerating modules.
Objective
To report combined oncological and functional outcome in a series of patients who underwent robot‐assisted radical prostatectomy (RARP) for clinically localised prostate cancer in a single ...European centre after 5‐year minimum follow‐up according to survival, continence and potency (SCP) outcomes.
Patients and Methods
We extracted from our prostate cancer database all consecutive patients with a minimum follow‐up of 5 years after RARP. Biochemical failure was defined as a confirmed PSA concentration of >0.2 ng/mL.
All patients alive at the last follow‐up were evaluated for functional outcomes using the Expanded Prostate Cancer Index Composite (EPIC) and Sexual Health Inventory for Men (SHIM) questionnaires.
Oncological and functional outcomes were reported according to the SCP system. Specifically, patients were classified as using no pad (C0), using one pad for security (C1), and using ≥1 pad (C2) (not including the prior definition).
Patients potent (SHIM score of >17) without any aids were classified as P0 category; patients potent (SHIM score of >17) with use of phosphodiesterase type 5 inhibitorsas P1; and patients with erectile dysfunction (SHIM score of <17) as P2 category. Patients who did not undergo a nerve‐sparing technique, who were not potent preoperatively, who were not interested in erections, or who did not have sexual partners were classified as Px category.
Results
The 3‐, 5‐ and 7‐year biochemical recurrence‐free survival rates were 96.3%; 89.6% and 88.3%, respectively.
At follow‐up, 146 (79.8%) were fully continent (C0), 20 (10.9%) still used a safety pad (C1) and 17 (9.3%) were incontinent using ≥1 pad (C2).
Excluding Px patients, 52 patients (47.3%) were classified as P0; 41 patients (37.3%) were classified as P1 and 17 patients (15.5%) were P2.
In patients preoperatively continent and potent, who received a nerve‐sparing technique and did not require any adjuvant therapy, oncological and functional success was attained by 77 (80.2%) patients.
In the subgroup of 67 patients not evaluable for potency recovery (Px), oncological and continence outcomes were attained in 46 patients (68.7%).
Conclusions
Oncological and functional success was attained in a high percentage of patients who underwent RARP at ≥5 years follow‐up.
Interestingly, this study confirmed that excellent oncological and functional outcomes can be obtained in the ‘best’ category of patients, i.e. those preoperatively continent and potent and with tumour characteristics suitable for a nerve‐sparing technique.
Abstract Background Several reports have shown that patients who undergo minimally invasive radical prostatectomy have a lower chance of undergoing pelvic lymph node dissection (PLND), irrespective ...of the disease characteristics. Objective We evaluated the rate and extension of PLND in patients who underwent robot-assisted radical prostatectomy (RARP). We tested the adherence of the indication for PLND to the European Association of Urology (EAU) guidelines. Design, setting, and participants Our study was a multi-institutional retrospective analysis of prospectively collected data on 2985 consecutive patients who underwent RARP at five high-volume European institutions. Patients were stratified according to preoperative cancer risk group. Intervention RARP. Outcome measurements and statistical analysis The rate and extent of PLND across different institutions were analyzed. Univariable and multivariable logistic regression models evaluated the association between preoperative variables and the probability of receiving PLND, as well as the presence of lymph node invasion (LNI). Finally, the probability of LNI was calculated for each patient, and the indication for PLND was compared with the EAU guidelines’ indications. Results and limitations A lymph node dissection was performed in 1777 patients (59.7%; 34.5% of low-risk patients, 64.9% of intermediate-risk patients, and 91.2% of high-risk patients). These rates were different across institutions: 5.0–41.4% in low-risk patients ( p < 0.001), 31.3–81.4% in intermediate-risk patients ( p < 0.001), and 84.6–96.4% in high-risk patients ( p = 0.06). The mean and median number of nodes removed was 10.8, and 122 patients (4.1%) had nodal metastases. At multivariable analysis, the institution represented an independent predictor of PLND ( p < 0.001). Of patients with current indication for PLND (EAU guidelines), 77.8% actually received the procedure. Limitations were the retrospective study design with different pathologic assessment and lack of follow-up data. Conclusions PLND is performed in a high proportion of patients undergoing RARP in high-volume centers in Europe for whom the procedure is indicated by the EAU guidelines, but significant differences exist among institutions. An effort toward a more rigorous standardization of PLND is advocated. Patient summary In this paper, we investigated the indication for and extension of pelvic lymph node dissection (PLND) in different institutions in Europe. Despite PLND being widely performed, significant variations with regard to PLND do exist among different institutions. Therefore, a thrust toward more rigorous attention to PLND is advocated.
Background: To investigate the impact of COVID-19 outbreak on the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). Methods: A retrospective analysis was performed using an ...Italian multi-institutional database of TURBT patients with high-risk urothelial NMIBC between January 2019 and February 2021, followed by Re-TURBT and/or adjuvant intravesical BCG. Results: A total of 2591 patients from 27 institutions with primary TURBT were included. Of these, 1534 (59.2%) and 1056 (40.8%) underwent TURBT before and during the COVID-19 outbreak, respectively. Time between diagnosis and TURBT was significantly longer during the COVID-19 period (65 vs. 52 days, p = 0.002). One thousand and sixty-six patients (41.1%) received Re-TURBT, 604 (56.7%) during the pre-COVID-19. The median time to secondary resection was significantly longer during the COVID-19 period (55 vs. 48 days, p < 0.0001). A total of 977 patients underwent adjuvant intravesical therapy after primary or secondary resection, with a similar distribution across the two groups (n = 453, 86% vs. n = 388, 86.2%). However, the proportion of the patients who underwent maintenance significantly differed (79.5% vs. 60.4%, p < 0.0001). Conclusions: The COVID-19 pandemic represented an unprecedented challenge to our health system. Our study did not show significant differences in TURBT quality. However, a delay in treatment schedule and disease management was observed. Investigation of the oncological impacts of those differences should be advocated.
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