Is trimodal therapy the current standard for muscle-invasive bladder cancer?

OBJECTIVE: The aim of this review is to summarize the current evidence and future perspectives of bladder-sparing treatment for MIBC. METHODS: A non-systematic literature search in Medline/Pubmed was performed in October 2023 with the following keywords "bladder cancer", "bladder-sparing", "trimodal therapy", "chemoradiation", "biomarkers", "immunotherapy", "neoadjuvant chemotherapy", "radiotherapy". RESULTS: Urology guidelines recommend radical cystectomy as the standard curative treatment for muscle-invasive urothelial bladder cancer, reserving radiotherapy for patients who are unfit or who want to preserve their bladder. Given the morbidity and mortality of cystectomy and its impact on quality of life and bladder function, modern oncologic therapies are increasingly oriented toward organ preservation and maximizing functional outcomes while maintaining treatment efficacy. Trimodal therapy, which incorporates maximal transurethral resection followed by radiotherapy with concurrent radiosensitizing chemotherapy, is an effective regimen for bladder function preservation in well-selected patients. Despite the absence of comparative data from randomized trials, the two approaches seem to provide comparable oncologic outcomes. Studies are evaluating the expansion of eligibility criteria for trimodal therapy, the optimization of radiotherapy and immunotherapy delivery to further improve outcomes, and the validation of biomarkers to guide bladder preservation. CONCLUSIONS: Trimodal therapy has shown acceptable outcomes for bladder preservation; therefore, it provides a valid treatment option in well-selected patients.

Enhancing Androgen Deprivation Therapy (ADT) integration in prostate cancer: Insights for Stereotactic Body Radiotherapy (SBRT) and brachytherapy modalities.

The utilization of Androgen Deprivation Therapy (ADT) in conjunction with Stereotactic Body Radiotherapy (SBRT) and Brachytherapy (BT) boost in prostate cancer treatment is a subject of ongoing debate and evolving clinical practice. While contemporary trends lean towards underutilizing ADT with these modalities, existing evidence suggests that its omission may lead to potentially inferior oncologic outcomes. Recommendations for ADT use should be patient-centric, considering individual risk profiles and comorbidities, with a focus on achieving optimal oncologic outcomes while minimizing potential side effects. Ongoing clinical trials, such as PACE-C, SPA, SHIP 0804, and SHIP 36B, are anticipated to provide valuable insights into the optimal use and duration of ADT in both SBRT and BT settings. Until new evidence emerges, it is recommended to initiate ADT for unfavorable intermediate-risk and high-risk prostate cancer patients undergoing radiotherapy, with a minimum duration of 6 months for unfavorable intermediate-risk patients and at least 12 months for those with high-risk characteristics. The decision to incorporate ADT into these radiation therapy modalities should be individualized, acknowledging the unique needs of each patient and emphasizing a tailored approach to achieve the best possible oncologic outcomes.

3D simulation of conductive nanofilaments in multilayer h-BN memristors via a circuit breaker approach.

A 3D simulation of conductive nanofilaments (CNFs) in multilayer hexagonal-BN memristors is performed. To do so, a simulation tool based on circuit breakers is developed including for the first time a 3D resistive network. The circuit breakers employed can be modeled with two, three and four resistance states; in addition, a series resistance and a module to account for quantum effects, by means of the quantum point contact model, are also included. Finally, to describe real dielectric situations, regions with a high defect density are modeled with a great variety of geometrical shapes to consider their influence in the resistive switching (RS) process. The simulator has been tuned with measurements of h-BN memristive devices, fabricated with chemical-vapour-deposition grown h-BN layers, which were electrically and physically characterized. We show the formation of CNFs that produce filamentary charge conduction in our devices. Moreover, the simulation tool is employed to describe partial filament rupture in reset processes and show the low dependence of the set voltage on the device area, which is seen experimentally.

Clinical Usefulness of Prostate-specific Membrane Antigen-ligand Positron Emission Tomography/Computed Tomography for the Detection of Prostate Cancer Biochemical Recurrence after Primary Radiation Therapy in Patients with Prostate-specific Antigen Below the Phoenix Threshold: Systematic Review and Meta-analysis.

AIMS: After primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the nadir. Several studies have shown that prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) can help in detecting recurrence in patients with low PSA values. This study aimed to assess the detection rate and patterns of PSMA-ligand PET/CT uptake in patients with suspected biochemical recurrence after primary radiotherapy and with PSA levels below the Phoenix threshold. MATERIALS AND METHODS: The meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Articles providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with a PSA value below the Phoenix threshold and who underwent PSMA-ligand PET/CT were included. Quality assessment was carried out using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). RESULTS: In total, five studies were included, recruiting 909 patients (202 with PSA ≤2 ng/ml). The PSMA-ligand detection rate in the patients with ≤2 ng/ml ranged from 66 to 83%. The most frequent source of PSMA-ligand PET/CT uptake was local recurrence, followed by lymph node metastasis and bone metastasis. PSMA-ligand PET/CT uptake due to local-only recurrence was more likely in patients with PSA ≤2 ng/ml compared with PSA > 2 ng/ml: risk ratio 0.72 (95% confidence interval 0.58-0.89), P = 0.003. No significant differences were observed in the detection of PSMA-ligand uptake in other areas. Limitations include a lack of biopsy confirmation, cohort reports with small sample sizes and a potentially high risk of bias. CONCLUSION: A significant detection of PSMA-ligand-avid disease was observed in patients with PSA levels below the Phoenix threshold. There was a higher likelihood of detecting local-only uptake when the PSA value was ≤2 ng/ml. The findings suggest that a critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT and highlight the need for further prospective trials.

Survival Differences of Patients with Resected Extraskeletal Osteosarcoma Receiving Two Different (Neo)Adjuvant Chemotherapy Regimens: A Systematic Review and Meta-analysis.

AIMS: Extraskeletal osteosarcoma (ESOS) is a malignant tumour developing in soft tissues, characterised by the production of osteoid or bone matrix by tumour cells. The standard treatment for localised ESOS is wide resection. Radiotherapy and chemotherapy are usually incorporated into the management of patients. Two types of chemotherapy regimen are mostly used: an osteosarcoma-type chemotherapy, based on cisplatin, and a soft-tissue sarcoma (STS)-type chemotherapy, using the combination of doxorubicin and ifosfamide. To investigate the difference in survival between these two chemotherapy regimens, a systematic review of studies reporting the 5-year disease-free survival (DFS) rates among patients with ESOS submitted to surgery and who received (neo)adjuvant chemotherapy with osteosarcoma-type or STS-type chemotherapy was carried out. MATERIALS AND METHODS: Of the 401 articles identified by systematically searching the PubMed, Embase and Cochrane Central Register of Controlled Trials databases, six retrospective studies were included in the final analysis. In total, 319 patients with localised/resected ESOS were included in the study. RESULTS: Our meta-analysis showed a benefit in 5-year DFS favouring the use of osteosarcoma-type chemotherapy (relative risk = 1.32, 95% confidence interval 1.03-1.69; P = 0.54); I2 heterogeneity was 0%. The 5-year DFS rate was 56.3% (95% confidence interval 48.3-64.3) with osteosarcoma-type chemotherapy and 45.2% (95% confidence interval 34.5-55.9) with STS-type chemotherapy, with I2 heterogeneity of 27% and 0%, respectively. CONCLUSIONS: Our analysis suggests that there may be a difference regarding the type of (neo)adjuvant chemotherapy regimen used in the treatment of patients with resected ESOS in favour of osteosarcoma-type chemotherapy. Future studies evaluating the role of this treatment modality in this scenario need to consider the type of chemotherapy regimen when comparing with an arm of surgery with/without radiotherapy alone.

Stereotactic Body Radiotherapy for Kidney Cancer: Ready for Prime Time?

The standard treatment for renal cell carcinoma (RCC) is surgery. However, a number of patients will not be candidates for surgical treatment or will reject this therapeutic approach. Therefore, alternative approaches are required. Historically, radiotherapy has been considered an ineffective treatment for RCC due to the radioresistance of renal tumour cells to conventional fractionation and the increased rate of toxicity. Stereotactic body radiotherapy (SBRT) is a radiotherapy technique that provides a non-invasive ablative treatment with remarkable rates of local control in both primary tumours and metastases in several locations, with a low associated morbidity due to the highly conformal dose and the use of image-guided techniques. Current evidence shows that a higher dose per fraction, achieving a higher biological effective dose, can overcome the radioresistance of RCC cells. Therefore, SBRT, as well as the combination of SBRT and new emerging immune therapies, has a potential role in the local treatment of primary RCC and oligometastatic RCC patients.

Development of secretome-based strategies to improve cell culture protocols in tissue engineering.

Advances in skin tissue engineering have promoted the development of artificial skin substitutes to treat large burns and other major skin loss conditions. However, one of the main drawbacks to bioengineered skin is the need to obtain a large amount of viable epithelial cells in short periods of time, making the skin biofabrication process challenging and slow. Enhancing skin epithelial cell cultures by using mesenchymal stem cells secretome can favor the scalability of manufacturing processes for bioengineered skin. The effects of three different types of secretome derived from human mesenchymal stem cells, e.g. hADSC-s (adipose cells), hDPSC-s (dental pulp) and hWJSC-s (umbilical cord), were evaluated on cultured skin epithelial cells during 24, 48, 72 and 120 h to determine the potential of this product to enhance cell proliferation and improve biofabrication strategies for tissue engineering. Then, secretomes were applied in vivo in preliminary analyses carried out on Wistar rats. Results showed that the use of secretomes derived from mesenchymal stem cells enhanced currently available cell culture protocols. Secretome was associated with increased viability, proliferation and migration of human skin epithelial cells, with hDPSC-s and hWJSC-s yielding greater inductive effects than hADSC-s. Animals treated with hWJSC-s and especially, hDPSC-s tended to show enhanced wound healing in vivo with no detectable side effects. Mesenchymal stem cells derived secretomes could be considered as a promising approach to cell-free therapy able to improve skin wound healing and regeneration.

SELNET clinical practice guidelines for bone sarcoma.

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context.

Nanostructured fibrin-based hydrogel membranes for use as an augmentation strategy in Achilles tendon surgical repair in rats.

Hydrogels are polymeric biomaterials characterised by their promising biological and biomechanical properties, which make them potential alternatives for use in tendon repair. The aim of the present study was to generate in vitro, and determine the therapeutic efficacy in vivo, of novel nanostructured fibrin-based hydrogels to be used as an augmentation strategy for the surgical repair of rat Achilles tendon injuries. Fibrin, fibrin-agarose and fibrin-collagen nanostructured hydrogels (NFH, NFAH and NFCH, respectively) were generated and their biomechanical properties and cell-biomaterial interactions characterised ex vivo. Achilles tendon ruptures were created in 24 adult Wistar rats, which were next treated with direct repair (control group) or direct repair augmented with the generated biomaterials (6 rats/group). After 4 and 8 weeks, the animals were euthanised for macroscopical and histological analyses. Biomechanical characterisation showed optimal properties of the biomaterials for use in tendon repair. Moreover, biological analyses confirmed that tendon-derived fibroblasts were able to adhere to the surface of the generated biomaterials, with high levels of viability and functionality. In vivo studies demonstrated successful tendon repair in all groups. Lastly, histological analyses disclosed better tissue and extracellular matrix organisation and alignment with biomaterial-based augmentation strategies than direct repair, especially when NFAH and NFCH were used. The present study demonstrated that nanostructured fibrin-collagen hydrogels can be used to enhance the healing process in the surgical repair of tendon ruptures.

Irrigation and phosphorous fertilization management to minimize rice grain arsenic content.

This research sought to minimize inorganic arsenic levels in polished rice grain by using different irrigation and phosphorous fertilization practices while also maintaining crop yield and water productivity. Two experiments were conducted during seasons 2018-2019 and 2019-2020 using a split-plot design with three blocks, five irrigation treatments (main-plots) and two phosphorous levels (sub-plots). Irrigation treatments consisted of a traditional continuous flood (CF) control and four alternatives irrigation techniques with one or two drying events during the irrigation cycle. The phosphorous fertilization levels investigated were an unfertilized control (0 kg P2O5 ha-1) and the recommended fertilization level of 50 kg P2O5 ha-1. Soil pH and redox potentials were measured in each treatment. Strategically-timed, low severity drying events were effective at achieving aerobic soil conditions, resulting in Eh values over 50 mV. The alternative irrigation treatment with two drying events, implemented at panicle initiation and full flowering, was the most effective in reducing inorganic arsenic in grain without affecting grain yield or the amount of irrigation water applied. This irrigation technique could be considered as an alternative management to the traditional continuous flooded to reach minimal inorganic arsenic accumulation in grain in order to attend special quality standards or specific market requirements. Accumulated inorganic arsenic in grain was below international maximum levels in all analyzed samples, with an average value of 0.084 mg kg-1.

Regional variability of arsenic content in Uruguayan polished rice.

Characterization of the country internal variability of arsenic (As) accumulation in rice grain across different rice production regions is very important in order to analyze its compliance with international and regional limits. A robust sampling study scheme (n = 150 samples) was performed to determine total arsenic (tAs) and inorganic (iAs) levels from polished rice grain covering all rice producing regions along two growing seasons. The mean and median concentration of tAs were 0.178 mg kg-1 and 0.147 mg kg-1, with a minimum and maximum value of 0.015 mg kg-1 and 0.629 mg kg-1, respectively and a coefficient of variation of 63.6%. The mean and median concentration of iAs were 0.062 mg kg-1 and 0.055 mg kg-1 respectively ranging from 0.005 mg kg-1 up to a maximum of 0.195 mg kg-1 and a coefficient of variation of 51.5%. A moderate correlation was revealed within iAs and tAs. Levels of iAs in all of the samples were below the international limits of 0.2 mg kg-1 according to the international limits for human health by the Codex Alimentarius (FAO and WHO, 2019). Rice fields cultivated on soils originated from igneous geological material reported lower arsenic levels accumulated in rice grain in relation to sedimentary soils. Japonica cultivars presented significantly lower tAs and iAs concentrations than Indica ones (p = 0.0121 and p < 0.0001; respectively). Consumption of rice by male and female adults in Uruguay is safe according to its level of annual consumption and based on the mean iAs levels determined in this study.

SEOR SBRT-SG stereotactic body radiation therapy consensus guidelines for non-spine bone metastasis.

The use of stereotactic body radiation therapy (SBRT) to treat non-spine bone metastases (NSBM) is becoming increasingly common in clinical practice. The clinical advantages of SBRT include good pain control and high local control rates, although only limited data are available. The Spanish Society of Radiation Oncology (SEOR) SBRT group recently convened a task force of experts in the field to address key questions related to SBRT for NSBM, including treatment indications, planning, techniques, and dose fractionation. The task force reviewed the available literature to develop evidence-based recommendations for the safe application of NSBM SBRT and to standardize and optimize SBRT processes. The present document provides a comprehensive analysis of the available data, including ongoing clinical trials and controversies, providing clinically applicable recommendations.

SEOR SBRT-SG survey on SRS/SBRT dose prescription criteria in Spain

Aim Stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) are essential tools in radiation oncology. In Spain, the use of these techniques continues to grow as older linear accelerators (linacs) are replaced with modern equipment. However, little is known about inter-centre variability in prescription and dose heterogeneity limits. Consequently, the SBRT-Spanish Task Group (SBRT-SG) of the Spanish Society of Radiation Oncology (SEOR) has undertaken an initiative to assess prescription and homogeneity in SRS/SBRT treatment. In the present study, we surveyed radiation oncology (RO) departments to obtain a realistic overview of prescription methods used for SBRT and SRS treatment in Spain. Methods A brief survey was developed and sent to 34 RO departments in Spain, mostly those who are members of the SEOR SBRT-SG. The survey contained seven questions about the specific prescription mode, dose distribution heterogeneity limits, prescription strategies according to SRS/SBRT type, and the use of IMRT–VMAT (Intensity Modulated Radiation Therapy–Volumetric Modulated Arc Therapy). Results Responses were received from 29 centres. Most centres (59%) used the prescription criteria D95% ≥ 100%. Accepted dose heterogeneity was wide, ranging from 107 to 200%. Most centres used IMRT–VMAT (93%). Conclusions This survey about SRS/SBRT prescription and dose heterogeneity has evidenced substantial inter-centre variability in prescription criteria, particularly for intended and accepted dose heterogeneity. These differences could potentially influence the mean planning target volume dose and its correlation with treatment outcomes. The findings presented here will be used by the SEOR SBRT-SG to develop recommendations for SRS/SBRT dose prescription and heterogeneity (AU)

Underreporting of mesothelioma, asbestosis and pleural plaques in Brazil.

BACKGROUND: Brazil has a long history of heavy asbestos consumption. However, the number of asbestos-related diseases (ARDs) falls far below the one expected compared with other asbestos consumer countries. AIMS: To examine underreporting of ARDs, that is mesothelioma, asbestosis and pleural plaques, in Brazil's Mortality Information System (SIM). METHODS: Health information systems (HIS) were mapped, datasets retrieved and records of ARD deaths extracted. Records were pair-matched using anonymous linkage to create a single database. ARD-reported cases missing in SIM were considered unreported. The study's period ranged from 2008 to 2014, when every HIS contributed to the ARD records pool. RESULTS: A total of 1298 registered ARD deaths were found, 996 cases of mesothelioma (77%) and 302 (23%) of asbestosis and pleural plaques. SIM was the major single data source of ARD but 335 mesothelioma deaths were missing, an average underreporting of 33%, with no clear time trend. For asbestosis and pleural plaques, underreporting of ARD oscillated from 55% in 2010 to 25% in 2014, a declining trend. ARD underreporting was not associated with sex or age. CONCLUSIONS: One-third of underreported ARD deaths in the universal SIM is unacceptably high and, apparently, it has not been improving substantially over time. After recoveries from multiple databases, the number of cases is still below, which could be expected based on asbestos consumption. Interoperability of multiple information systems could enhance case detection and improve the precision of mortality estimates, which are crucial for surveillance and for evaluation of remedial policies.

Recommended procedures and responsibilities for radiosurgery (SRS) and extracranial stereotactic body radiotherapy (SBRT): report of the SEOR in collaboration with the SEFM

Today, patient management generally requires a multidisciplinary approach. However, due to the growing knowledge base and increasing complexity of Medicine, clinical practice has become even more specialised. Radiation oncology is not immune to this trend towards subspecialisation, which is particularly evident in ablative radiotherapy techniques that require high dose fractions, such as stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). The aim of the present report is to establish the position of the Spanish Society of Radiation Oncology (SEOR), in collaboration with the Spanish Society of Medical Physics (SEFM), with regard to the roles and responsibilities of healthcare professionals involved in performing SRS and SBRT. The need for this white paper is motivated due to the recent changes in Spanish Legislation (Royal Decree [RD] 601/2019, October 18, 2019) governing the use and optimization of radiotherapy and radiological protection for medical exposure to ionizing radiation (article 11, points 4 and 5) [1 ], which states: “In radiotherapy treatment units, the specialist in Radiation Oncology will be responsible for determining the correct treatment indication, selecting target volumes, determining the clinical radiation parameters for each volume, directing and supervising treatment, preparing the final clinical report, reporting treatment outcomes, and monitoring the patient’s clinical course.” Consequently, the SEOR and SEFM have jointly prepared the present document to establish the roles and responsibilities for the specialists—radiation oncologists (RO), medical physicists (MP), and related staff —involved in treatments with ionizing radiation. We believe that it is important to clearly establish the responsibilities of each professional group and to clearly establish the professional competencies at each stage of the radiotherapy process (AU)