Toxicity profile and Patient-Reported outcomes following salvage Stereotactic Ablative Radiation Therapy to the prostate Bed: The POPART multicentric prospective study.

Background: While SBRT to the prostate has become a valuable option as a radical treatment, limited data support its use in the postoperative setting. Here, we report the updated results of the multicentric Post-Prostatectomy Ablative Radiation Therapy (POPART) trial, investigating possible predictors of toxicities and patient-reported outcomes. Methods: Patients with PSA levels between 0.1-2.0 ng/mL after radical prostatectomy received Linac-based SBRT to the prostate bed in five fractions every other day for a total dose of 32.5 Gy (EQD21.5 = 74.3 Gy). Late toxicity was assessed using CTCAE v.5 scale, while EPIC-CP, ICIQ-SF, IIEF 5 questionnaires and PSA levels measured quality of life and biochemical control. Pre- and post-treatment scores were compared using a paired t-test, with MID established at > 0.5 pooled SD from the baseline. A logistic regression analysis was performed to evaluate potential associations between specific patient/tumor/treatment factors and outcome deterioration. Results: From April 2021 to April 2023 a total of 50 pts were enrolled and treated. Median follow-up was 12.2 (3-27) months. No late ≥ G2 GI or GU toxicity was registered. Late G1 urinary and rectal toxicities occurred in 46 % and 4 % of patients, respectively. Among 47 patients completing all EPIC-CP domains, four (9 %) showed worsened QoL, and eleven (26 %) developed erectile dysfunction correlating with PTV D2% (P = 0.032). At Multivariate analysis bladder wall D10cc independently correlated with late G1 GU toxicity (P = 0.034). Median post-treatment PSA nadir was 0.04 ng/mL (0.00 - 0.84). At the last follow-up, six patients presented with biochemical failure, including two nodal relapses. Conclusions: Our findings show that post-prostatectomy SBRT did not result in increased toxicity nor a significant decline in QoL measures, thus showing that it can be safely extended to the postoperative setting. Long-term follow-up and randomized comparisons with different RT schedules are needed to validate this approach.

Comparison of derived correction factors for effects of ion recombination and photon beam quality index following TG-51 and TRS-398 dosimetry protocols.

In this study, ion recombination correction factor (kS) and beam quality conversion factor ( [Formula: see text] ) values were extracted following the recommendations of the TRS-398 and TG-51 dosimetry protocols for widely used cylindrical ionization chambers for high energy photon beam dosimetry to quantify the agreement between the instructions for these two protocols for absolute dosimetry inside water. Four different types of cylindrical ionization chambers comprising Farmer (TM30013), Semiflex 0.125 cm3 (TM31010), Semiflex 0.3 cm3 (TM31013), and PinPoint (TM31016) were considered, and kS and [Formula: see text] values were determined at photon energies of 6 MV and 15 MV. The maximum difference between the measured kS values according to the instructions in the TRS-398 and TG-51 protocols was 0.03%. The kS data measured with both protocols agreed well with those measured by using the Jaffe-plot approach, where the maximum difference was about 0.33%. The observed differences between the [Formula: see text] factors measured by using the TRS-398 and TG-51 dosimetry protocols at photon energies of 6 MV and 15 MV were 0.37% and 0.55%, respectively. The [Formula: see text] values measured using the TG-51 dosimetry protocols were slightly closer to those measured by a reference ionization chamber dosimeter. We conclude that the maximum differences were about 0.4% and 0.6% in the absorbed dose measurements according to the TRS-398 and TG-51 instructions at photon energies of 6 MV and 15 MV, respectively. The type of ionization chamber employed also affected the differences, where the maximum and minimum dose differences were found using the Farmer and PinPoint chambers, respectively.

On the measurement of scaling factors in the RW3 plastic phantom during high energy electron beam dosimetry.

Ionometric electron dosimetry inside water-equivalent plastic phantoms demands special considerations including determination of depth scaling and fluence scaling factors (cpl and hpl) to shift from in-phantom measurements to those relevant to water. This study evaluates these scaling factors for RW3 slab phantom and also introduces a new coefficient, k(RW3), for direct conversion from RW3 measurements to water without involving scaling factors. The RW3 solid phantom developed by the PTW Company was used and the corresponding scaling factors including cpl, hpl, and k(RW3) were measured for conventional electron energies of 4, 6, 9, 12, and 16 MeV. Separate measurements were performed in water and the RW3 slab phantom using the Advanced Markus chamber. The validity of the reported scaling factors was confirmed by comparing the direct and indirect percentage depth dose (PDD) measurements in water and in the RW3 phantom. The cpl values for the RW3 phantom were respectively equal to 0.915, 0.927, 0.934, 0.937, and 0.937 for 4, 6, 9, 12, and 16 MeV electron energies. The hpl and k(RW3) values were dependent on the depth of investigation and electron energy. Application of the cpl-hpl factors and k(RW3) coefficients to measured data inside the RW3 can reliably reproduce the measured PDD curves in water. The mean difference between the PDDs measured directly and indirectly in water and in the RW3 phantom was less than 1.2% in both approaches for PDD conversion (cpl-hpl coupling and the use of k(RW3)). The measured scaling factors and k(RW3) coefficients are sufficiently relevant to mimic water-based dosimetry results through indirect measurements inside the RW3 slab phantom. Nevertheless, employing k(RW3) is more straightforward than the cpl-hpl approach because it does not involve scaling and it is also less time-consuming.

A rare event of perioperative spinal subarachnoid hemorrhage in mixed connective tissue disease: a case report.

Background: Spinal subarachnoid hemorrhage (SSH) is an extremely rare event and its causes include trauma, vascular malformation, anticoagulant therapy, and autoimmune disease. Although connective disorders are associated with an increased risk of cerebral subarachnoid hemorrhage (SAH), to our knowledge, the occurrence of SSH associated with mixed connective tissue disease (MCTD) have not been addressed in the literature. We report the unique occurrence of SSH in a patient with anti-U1 ribonucleoprotein (U1-RNP) and anti-nuclear antibodies (ANA) positive MCTD triggered by abdominal surgery. Case Description: A 69-year-old woman with MCTD was admitted to our hospital because of vomiting and abdominal pain. Surgical treatment of adhesion ileus with small bowel resection was followed on the second postoperative day by sudden back pain radiating to the legs and abdominal belt-shaped lumbar exanthema. A spinal anesthesia was not performed. Neurological examination revealed loss of sensation and muscle strength in both legs. Magnetic resonance imaging (MRI) showed an SSH beyond T6 and the lumbosacral junction with ventral displacement of the spinal cord without myelopathy. Rapid improvement in motor function and sensitivity allowed a conservative management. The patient recovered successfully and was discharged without neurological deficits. Conclusions: We postulate that vascular rupture causing SSH was triggered by perioperative increased intraluminal abdominal pressure combined with fragility of the spinal arachnoid mater due to MCTD. The decision to undergo a conservative treatment of the SSH was triggered by the rapid improvement of the neurological presentation and the disappearance of symptoms in a few days. We recommend caution in patients with connective tissue diseases who undergo thoracic or abdominal surgery and be aware for neurosurgeons that SSH is possible although rare and that conservative treatment may be considered.

Acute Toxicity and Quality of Life in a Post-Prostatectomy Ablative Radiation Therapy (POPART) Multicentric Trial.

BACKGROUND: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). METHODS: Patients with post-radical prostatectomy PSA levels of ≥0.1-2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. RESULTS: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55-82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18-1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0-0.48 ng/mL). CONCLUSIONS: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy.

High-Affinity Cu(I)-Chelator with Potential Anti-Tumorigenic Action-A Proof-of-Principle Experimental Study of Human H460 Tumors in the CAM Assay.

Human lung cancer ranks among the most frequently treated cancers worldwide. As copper appears critical to angiogenesis and tumor growth, selective removal of copper represents a promising strategy to restrict tumor growth. To this end, we explored the activity of the novel high-affinity membrane-permeant Cu(I) chelator PSP-2 featuring a low-zeptomolar dissociation constant. Using H460 human lung cancer cells, we generated small tumors on the chorioallantoic membrane of the chicken embryo (CAM assay) and studied the effects of topical PSP-2 application on their weight and vessel density after one week. We observed a significant angiosuppression along with a marked decrease in tumor weight under PSP-2 application compared to controls. Moreover, PSP-2 exposure resulted in lower ki67+ cell numbers at a low dose but increased cell count under a high dose. Moreover, HIF-1α+ cells were significantly reduced with low-dose PSP-2 exposure compared to high-dose and control. The total copper content was considerably lower in PSP-2 treated tumors, although statistically not significant. Altogether, PSP-2 shows promising potential as an anti-cancer drug. Nevertheless, further animal experiments and application to different tumor types are mandatory to support these initial findings, paving the way toward clinical trials.

Hybrid nanocomposite as a chest wall graft with improved vascularization by copper oxide nanoparticles.

Chest wall repair can be necessary after tumor resection or chest injury. In order to cover or replace chest wall defects, autologous tissue or different synthetic materials are commonly used, among them the semi-rigid gold standard Gore-Tex® and prolene meshes. Synthetic tissues include composite materials with an organic and an inorganic component. On the basis of previously reported hybrid nanocomposite poly-lactic-co-glycolic acid amorphous calcium phosphate nanocomposite (PLGA/aCaP), a CuO component was incorporated to yield (60%/35%/5%). This graft was tested in vitro by seeding with murine adipose-derived stem cells (ASCs) for cell attachment and migration. The graft was compared to PLGA/CaCO3 and PLGA/hydroxyapatite, each providing the inorganic phase as nanoparticles. Further characterization of the graft was performed using scanning electron microscopy. Furthermore, PLGA/aCaP/CuO was implanted as a chest wall graft in mice. After 4 weeks, total cell density, graft integration, extracellular matrix components such as fibronectin and collagen I, the cellular inflammatory response (macrophages, F4/80 and lymphocytes, CD3) as well as vascularization (CD31) were quantitatively assessed. The nanocomposite PLGA/aCaP/CuO showed a good cell attachment and cells migrated well into the pores of the electrospun meshes. Cell densities did not differ between PLGA/aCaP/CuO and PLGA/CaCO3 or PLGA/hydroxyapatite, respectively. When applied as a chest wall graft, adequate stability for suturing into the thoracic wall could be achieved. Four weeks post-implantation, there was an excellent tissue integration without relevant fibrotic changes and a predominating collagen I matrix deposition within the graft. Slightly increased inflammation, reflected by increased infiltration of macrophages could be observed. Vascularization of the graft was significantly enhanced when compared with PLGA/aCaP (no CuO). We conclude that the hybrid nanocomposite PLGA/aCaP/CuO is a viable option to be used as a chest wall graft. Surgical implantation of the material is feasible and provides stability and enough flexibility. Proper tissue integration and an excellent vascularization are characteristics of this biodegradable material.

In-vitro investigation of cardiac implantable electronic device malfunction during and after direct photon exposure: A three-centres experience.

PURPOSE: Radiotherapy may cause malfunction of implantable cardioverter-defibrillators (ICDs) and pacemakers (PMs). We carried-out a multicentre randomized in-vitro study on 65 ICDs and 145 PMs to evaluate malfunctions during and after direct irradiation to doses up to 10 Gy. METHODS: Three centres equipped with different linear accelerator and treatment-planning systems participated in the study. Computed Tomography (CT) acquisitions were performed to build the treatment plans. All devices were exposed to dose of 2, 5, or 10 Gy (6 MV). All devices underwent a baseline examination and 64 wireless real-time telemetry-transmissions (47 ICDs and 17 PMs) were monitored during photon exposures. All devices were interrogated after exposure and once monthly for six subsequent months. RESULTS: Fifty-four of the 64 wireless-enabled CIEDs (84.4%) recorded noise-related interferences during exposure. In detail, 40/47 ICDs (85.1%) reported interference, of which 16 ICDs (34%) reported potentially clinically relevant pacing inhibition and inappropriate detections. Following exposure, a soft reset occurred in 1/145 PM (0.7%) while 7/145 PMs (4.8%) reported battery issues. During the six-month follow-up, 1/145 PM (0.7%) reported a soft reset, while 12/145 more PMs (8.3%) and 1/64 ICD (1.5%) showed abnormal battery depletion. All reported issues occurred independently of exposure dose. Finally, irreversible effects on software and battery life occurred in only non-MRI-compatible devices. CONCLUSION: ICDs mostly featured real-time transient sensing issues, while PMs mostly experienced long-term battery or software issues that were observed immediately following radiation exposure and during follow-up. Irreversible effects on battery life and software occurred in only non-MRI-compatible devices.

Comparing the dosimeter-specific corrections for influence quantities of some parallel-plate ionization chambers in conventional electron beam dosimetry.

The performance characteristics of some widely employed parallel-plate ionization chambers in dosimetry of conventional high energy electron beams were evaluated and compared in the present study following the recommendations of the IAEA TRS-398 reference dosimetry protocol. Three different types of PTW-made parallel-plate ionization chambers including Roos (TM34001), Markus (TM23343), and Advanced Markus (TM34045) were employed, and correction factors for polarity (kpol), recombination (ks), and quality conversion factor ( [Formula: see text] ) were determined at different nominal electron energies of 4, 6, 9, 12, 16, and 20 MeV produced by a Varian Trilogy clinical Linac. All measurements were performed inside a MP3-M automatic water phantom in the reference condition of 100 cm SSD (source to surface distance), reference measurement depth (zref), and 10 × 10 cm2 field size at the phantom surface. The maximum and minimum range of kpol deviations from unity were respectively found for Markus and Roos ionization chambers. The maximum ks values also belonged to the Markus ionization chamber, while the minimum ks values were observed for the Advanced Markus chamber. The measured ks values through recommendations of the TRS-398 dosimetry protocol were in good accordance with those obtained by Jaffe-plot analysis for all considered ionization chambers. The type of employed ionization chamber can minimally affect the measured electron beam quality index (R50), while it can have a more considerable impact on [Formula: see text] value, especially in the case of the Markus chamber. From the results, it can be concluded that the Roos and Advanced Markus ionization chambers have a superior performance in the case of electron beam dosimetry, although all considered ionization chambers fulfilled the criteria requested by relevant reference dosimetry protocols.

Evaluation of the uncertainty associated with the ion recombination correction in high dose-per-pulse electron beam dosimetry: an MC approach.

The high dose and dose-per-pulse rates (up to 130 mGy/pulse) produced by some intraoperative radiation therapy (IORT) accelerators pose specific dosimetric problems due to the high density of electric charge per pulse produced in the ionization chamber cavity. In particular, the correction factor for ion recombination, ks , calculated with the traditional two-voltage method is significantly overestimated and three alternative models have been proposed in the literature allowing for the presence of a free-electron component. However, at present there is no general consensus on the best model to assess the ion recombination correction and controversy remains on the uncertainty associated with k s . In the present work we adopted a Monte Carlo (MC) approach to assess the uncertainty associated with the ion recombination correction in plane-parallel chambers used in high dose-per-pulse electron beam dosimetry. The uncertainty associated with k s was calculated for the following plane-parallel ionization chambers: Scanditronix/Wellhofer Parallel Plate Chamber PPC05 and PPC40, PTW Advanced Markus Model 34 045 and PTW Roos Model 34 001. Input variables for MC calculations were derived from experimental data at 28 and 73 mGy/pulse. Taken together, the results of this study indicate that ks values calculated according to the three ion recombination models do not overlap within their standard uncertainties, suggesting that an additional type-B uncertainty component would be necessary to take into account possible differences between the models. Our results indicate that the combined relative standard uncertainty in k s should be calculated as the sum in quadrature of a (type-A) MC-based uncertainty component and a (type-B) uncertainty contribution evaluated assuming a uniform distribution between k s values obtained from the two extreme models.

Radiation exposure of an anaesthesiologist in catheterisation and electrophysiological cardiac procedures.

Sometimes, cardiac catheterisation and electrophysiological procedures, diagnostic and interventional, require an anaesthesiological support. The anaesthesiologist receives radiation doses depending on various factors, such as type of procedure and exposure modality, anaesthesiological technique, individual protective devices and operator experience. The aim of this study was to investigate the dose per procedure, the exposure inhomogeneity and the effective dose, E, of a senior anaesthesiologist in the haemodynamic laboratory of Ospedali Riuniti, Bergamo. The dose monitoring was routinely performed with sets of several thermoluminescent dosemeters and an electronic personal dosemeter. The study covered 300 consecutive procedures over 1 y. The anaesthesiologist wore a protective apron, a thyroid collar and glasses (0.5 mm lead-equivalent).