Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE).

BACKGROUND: Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series. MATERIALS AND METHODS: We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan-Meier survival curves and fitted univariate and multivariable Cox's proportional hazards regression models to study the association between the clinical variables and each survival type. RESULTS: At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3-99.6%) and 85.5% (95%CI 81.9-89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4-6%) and 6% (95%CI 4-8%), respectively. CONCLUSION: Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

Neuroprotective Potential of Dendritic Cells and Sirtuins in Multiple Sclerosis.

Myeloid cells, including parenchymal microglia, perivascular and meningeal macrophages, and dendritic cells (DCs), are present in the central nervous system (CNS) and establish an intricate relationship with other cells, playing a crucial role both in health and in neurological diseases. In this context, DCs are critical to orchestrating the immune response linking the innate and adaptive immune systems. Under steady-state conditions, DCs patrol the CNS, sampling their local environment and acting as sentinels. During neuroinflammation, the resulting activation of DCs is a critical step that drives the inflammatory response or the resolution of inflammation with the participation of different cell types of the immune system (macrophages, mast cells, T and B lymphocytes), resident cells of the CNS and soluble factors. Although the importance of DCs is clearly recognized, their exact function in CNS disease is still debated. In this review, we will discuss modern concepts of DC biology in steady-state and during autoimmune neuroinflammation. Here, we will also address some key aspects involving DCs in CNS patrolling, highlighting the neuroprotective nature of DCs and emphasizing their therapeutic potential for the treatment of neurological conditions. Recently, inhibition of the NAD+-dependent deac(et)ylase sirtuin 6 was demonstrated to delay the onset of experimental autoimmune encephalomyelitis, by dampening DC trafficking towards inflamed LNs. Thus, a special focus will be dedicated to sirtuins' role in DCs functions.

Radiotherapy treatment volumes for oligorecurrent nodal prostate cancer: a systematic review.

BACKGROUND: Radiotherapy is an emerging treatment strategy for nodal oligorecurrent prostate cancer (PCa) patients. However, large heterogeneities exist in the RT regimens used, with series reporting the use of elective nodal radiotherapy (ENRT) strategies and others the delivery of focal treatments to the relapsing nodes with Stereotactic Body Radiotherapy (SBRT). In this systematic review of the literature we compared the oncological outcomes and toxicity of the different RT regimens for nodal oligorecurrent PCa patients, with the aim of defining the optimal RT target volume in this setting. METHODS: We performed a systemic search on the Pubmed database to identify articles reporting on the use of ENRT or SBRT for oligometastatic PCa with nodal recurrence. RESULTS: Twenty-two articles were analyzed, including four prospective phase II trials (3 with SBRT and 1 with ENRT). Focal SBRT, delivered with an involved node, involved site, and involved field modality, was the most commonly used strategy with 2-year progression-free survival (PFS) rates ranging from 16 to 58% and a very low toxicity profile. Improved PFS rates were observed with ENRT strategies (52-80% at 3 years) compared to focal SBRT, despite a slightly higher toxicity rate. One ongoing randomized phase II trial is comparing both modalities in patients with nodal oligorecurrent PCa. CONCLUSIONS: With a large variability in patterns of practice, the optimal RT strategy remains to be determined in the setting of nodal oligorecurrent PCa. Ongoing randomized trials and advances in translational research will help to shed light on the best management for these patients. .

Whole breast external beam radiotherapy in elderly patients affected by left-sided early breast cancer: a dosimetric comparison between two simple free-breathing techniques.

BACKGROUND: Elderly breast cancer patients are frequently affected by significant comorbidities that make sophisticated radiotherapy treatments particularly challenging. AIMS: We dosimetrically analyzed two different simple free-breathing external beam radiotherapy (EBRT) techniques for the hypofractionated treatment of the left breast in elderly patients with a low compliance, to compare target coverage, and heart and left anterior descending coronary artery (LADCA) sparing. METHODS: We developed radiation plans for 24 elderly patients using 3D conformal (3DCRT) field-in-field tangential technique and intensity-modulated (IMRT) tangential beam technique. Dose-Volume-Histograms (DVHs) were used to provide a quantitative comparison between plans. RESULTS: The median breast volume was 645 cm3. IMRT and 3DCRT plans comparison demonstrated no significant differences in terms of organ sparing for the heart. Regarding LADCA, mean dose (10.3 ± 9.5 Gy vs 11.9 ± 9.6 Gy, p = 0.0003), maximum dose (26.1 ± 16.1 Gy vs 29.1 ± 16.1 Gy, p = 0.004) and V17 Gy (21.5% ± 26.9% vs 25.0% ± 27.2%, p = 0.002) significantly decreased using IMRT compared with 3DCRT. IMRT plans showed a better target coverage compared with 3DCRT (0.91 ± 0.05 vs 0.93 ± 0.04, p = 0.05). DISCUSSION: Comparing the two different EBRT techniques, we demonstrated few, although substantial, dosimetric differences in terms of doses to the organs at risk characterized by a statistically significant dose reduction of LADCA in the IMRT plans. CONCLUSIONS: Elderly patients with a low compliance to treatment might benefit from 3DCRT with field-in-field tangential arrangement or from a simple IMRT approach. IMRT should be preferred.

Oligometastatic cancer in elderly patients: the "blitzkrieg" radiotherapy approach : SBRT in oligometastatic elderly patients.

AIMS: To retrospectively evaluate the outcome of stereotactic body radiation therapy (SBRT) in the treatment of elderly patients affected by isolated body metastasis from different primitive tumors. METHODS: 70 patients with isolated body metastasis were treated. Median age at diagnosis was 75 years (IQR 69-80). The most common SBRT fractionation scheme was 5 × 7 Gy (total dose 35 Gy). The primary endpoints were Local Control (LC) and Toxicity. Secondary endpoints were Overall Survival (OS) and Disease-Specific Survival (DSS). Response to radiotherapy was assessed according to RECIST criteria v1.1. Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. We performed survival analysis with the Kaplan-Meier method. The correlation between time actuarial incidence and clinical parameters was studied. RESULTS: Median follow-up was 26.5 months. 44 patients (62.8%) were alive at the time of analysis, while 22 (31.4%) died because of the disease. Local control at 2 and 3 years was 87%. The 2-year OS and DSS were 84 and 71%, respectively, while the 3-year values were 57 and 62%. PFS at 2 and 3 years was 41 and 25%, respectively. On univariate analysis, KPS ≥ 90 is statistically correlated with improved OS and DSS (p < 0.05). Acute toxicity of grade ≥ 2 occurred in 4 (5.7%) patients, while late toxicity ≥ 2 was recorded in 6 (8.6%) patients. CONCLUSIONS: Ablative Radiotherapy represents a safe, effective, and minimally invasive treatment modality for elderly oligometastatic patients who are judged unfit for systemic therapy.

Volumetric image-guided conformal radiotherapy for localized prostate cancer: Analysis of dosimetric and clinical factors affecting acute and late toxicity.

AIM: To identify factors influencing toxicity in patients affected by localized prostate cancer treated with conformal image-guided radiotherapy. BACKGROUND: Image guidance in combination with conformal techniques is the standard of care in localized prostate cancer, but factors affecting toxicity are still under investigation. MATERIALS AND METHODS: 294 patients were analyzed. Median age at diagnosis was 71 year. 76 Gy (38 × 2 Gy) were delivered to the target volume. We used the χ2 test to analyse associations between toxicity and dosimetric and clinical parameters. Multivariate analysis was performed using binary logistic regression. Kaplan-Meier method was used for survival analysis. RESULTS: Median follow-up was 62.9 months. Acute grade ≥2 gastro-intestinal toxicity (GI) was 12.1%. Acute genito-urinary (GU) toxicity of grade ≥2 was 33.9%. Actuarial 4 and 5 years late grade ≥2 GI was 3% and 4%, respectively. Four and 5-year late grade ≥2 GU toxicity was 6% and 10%. At multivariate analysis for acute toxicity rectal V70 was correlated with GI toxicity (p = 0.01, HR 2.73 CI 1.19-6.26), and smoking habit with GU toxicity (p < 0.01, HR 2.50 CI 1.51-4.14). For late toxicity, rectal V70 was correlated with gastro-intestinal toxicity (p = 0.04, HR 4.76 CI 1.07-21.13), and pre-radiotherapy urinary symptoms with genito-urinary toxicity (p = 0.01, HR 2.84 CI 1.29-6.22). DISCUSSION: Conformal image-guided radiotherapy shows low rates of toxicity. Smoking should be avoided during radiotherapy. Besides the evaluation of high doses received by the organs at risk, individual factors, such as co-morbidities and lifestyle choices, have an impact on normal-tissue complication risk.

A multi-methodological evaluation approach for assessing the impact of neighbourhood quality on public health.

Starting from a growing interest for urban neighbourhood health effects, the purpose of this paper is to suggest a multi-methodological approach for providing a comprehensive evaluation of the quality of open spaces under the urban design perspective. Despite the growing body of research and empirical evidence about the relationship among quality of built environment and public health, there is still a lack of studies on urban quality assessment. This paper brings forward a multi-methodological approach for assessing the quality of open spaces by the assignment of a composite score. The study combines Geographic Information Systems (GIS) and Multi-Attribute Value Theory (MAVT) with the aim of proposing urban quality maps. Open spaces, including green and walkable areas, streets and squares are evaluated with respect to the following attributes: accessibility, liveability, vitality, and identity. The urban quality maps provide a robust basis to run different kind of analysis and to support cross-sectorial policies towards the improvement of public health.

Nerve-Glial antigen 2: unmasking the enigmatic cellular identity in the central nervous system.

Chondroitin sulfate proteoglycans (CSPGs) are fundamental components of the extracellular matrix in the central nervous system (CNS). Among these, the Nerve-Glial antigen 2 (NG2) stands out as a transmembrane CSPG exclusively expressed in a different population of cells collectively termed NG2-expressing cells. These enigmatic cells, found throughout the developing and adult CNS, have been indicated with various names, including NG2 progenitor cells, polydendrocytes, synantocytes, NG2 cells, and NG2-Glia, but are more commonly referred to as oligodendrocyte progenitor cells. Characterized by high proliferation rates and unique morphology, NG2-expressing cells stand apart from neurons, astrocytes, and oligodendrocytes. Intriguingly, some NG2-expressing cells form functional glutamatergic synapses with neurons, challenging the long-held belief that only neurons possess the intricate machinery required for neurotransmission. In the CNS, the complexity surrounding NG2-expressing cells extends to their classification. Additionally, NG2 expression has been documented in pericytes and immune cells, suggesting a role in regulating brain innate immunity and neuro-immune crosstalk in homeostasis. Ongoing debates revolve around their heterogeneity, potential as progenitors for various cell types, responses to neuroinflammation, and the role of NG2. Therefore, this review aims to shed light on the enigma of NG2-expressing cells by delving into their structure, functions, and signaling pathways. We will critically evaluate the literature on NG2 expression across the CNS, and address the contentious issues surrounding their classification and roles in neuroinflammation and neurodegeneration. By unraveling the intricacies of NG2-expressing cells, we hope to pave the way for a more comprehensive understanding of their contributions to CNS health and during neurological disorders.

Urethra-Sparing Prostate Cancer Stereotactic Body Radiation Therapy: Sexual Function and Radiation Dose to the Penile Bulb, the Crura, and the Internal Pudendal Arteries From a Randomized Phase 2 Trial.

PURPOSE: Erectile dysfunction (ED) is a common side effect after prostate cancer stereotactic body radiation therapy (SBRT). We aimed to assess the correlation between the dose to the penile bulb (PB), internal pudendal arteries (IPA), and crura with the development of ED after ultrahypofractionation as part of a phase 2 clinical trial of urethra-sparing prostate SBRT. METHODS AND MATERIALS: Among the 170 patients with localized prostate cancer from 9 centers included in the trial, 90 men with Common Terminology Criteria for Adverse Events version 4.03 grade 0 to 1 ED (ED-) at baseline treated with 36.25 Gy in 5 fractions were selected for the present analysis. Doses delivered to the PB, crura, and IPA were analyzed and correlated with grade 2 to 3 ED (ED+) development. The effect on quality of life, assessed by the European Organisation for Research and Treatment of Cancer (EORTC QLQ-PR25) questionnaire, was reported. RESULTS: After a median follow-up of 6.5 years, 43% (n = 39) of the patients developed ED+, and 57% (n = 51) remained ED-. The dose delivered to the crura was significantly higher in ED+ patients than in ED- patients (7.7 vs 3.6 Gy [P = .014] for the Dmean and 18.5 vs 7.2 Gy [P = .015] for the D2%, respectively). No statistically significant difference between ED+ and ED- patients was observed for the dose delivered to the PB and IPA. The median ED+-free survival was worse in patients receiving a crura Dmean ≥ 4.7 versus < 4.7 Gy (51.5% vs 71.7%, P = .005) and a crura D2% > 12 versus ≤ 12 Gy (54.9% vs 68.9%, P = .015). No ED+-free survival differences were observed for doses delivered to the PB and IPA. Decline in EORTC QLQ-PR25 sexual functioning was significantly more pronounced in patients with higher doses to the crura. CONCLUSIONS: By keeping a Dmean and D2% to crura below 4.7 and 12 Gy, respectively, the risk of developing ED+ after prostate SBRT may be significantly reduced.

The Prognostic Value of DCE-MRI Findings before Salvage Radiotherapy after Radical Prostatectomy.

BACKGROUND: To investigate the predictive role of dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) findings before salvage radiotherapy after radical prostatectomy (RP). METHODS: This retrospective study selected patients with biochemical failure (BF) after RP restaged with DCE-MRI. Patients underwent sRT in 30 fractions delivering 66-69 Gy and 73.5 Gy to the prostatic fossa and to the local failure as per DCE-MRI, respectively. Pelvic nodes were treated to 54 Gy in selected patients. The endpoint was BF after sRT. RESULTS: In total, 236 patients were analyzed and 146 (61.9%) had presumed local failure at DCE-MRI: 54.8%, 23.8% and 21.4% were found at the vesico-urethral anastomosis (VUA), the bladder neck and the retro-vesical space, respectively. The presence of a local failure at DCE-MRI halved the risk of BF; VUA-only location and lesion volume were independently correlated with survival without evidence of biochemical failure (bNED) at multivariable analysis. For patients with VUA-only disease up to 0.4 cc, the 4-year-bNED was 94.6% (95%CI: 80.2-98.6%) as opposed to 80.9% (95%CI: 71.6-87.4%) and 73.7% (95%CI: 63.1-81.8%) for other lesions and no macrodisease, respectively. CONCLUSIONS: DCE-MRI at restaging for BF after RP provides predictive and therapeutic information. Patients with small lesions at the VUA have an excellent prognosis after sRT.

Stereotactic Ablative Radiation Therapy in 3 Fractions Induces a Favorable Systemic Immune Cell Profiling in Prostate Cancer Patients.

The impact of radiotherapy (RT) on immune cell status in prostate cancer (PCa) is only partially determined. The aim of this study was to assess the effect of different RT strategies on peripheral B, T, and Natural killer (NK) lymphocytes at precise longitudinal time-points in PCa. 18 patients treated with stereotactic body radiation therapy (SBRT) (40 Gy/3FRX), definitive moderate-hypofractionation (62 Gy/20FRX), or post-operative conventional-fractionation RT (66-69 Gy/30FRX) were prospectively evaluated for the immune cell profile in terms of immune cell composition, differentiation stage, cytokine production and inhibitory receptor (IR) expression. The immune-monitoring of the 18 patients revealed that RT affects the balance of systemic immune cells, with the main differences observed between SBRT and conventionally fractionated RT. SBRT favorably impacts immune response in term of increased B cells, central-memory and effector-memory CD8+ T cells, along with decreased Treg cells after treatment. On the contrary, conventional fractionated RT had a long-term negative effect on the systemic immune profile, including a decrease of total lymphocyte counts accompanied by an increase of neutrophils-to-lymphocytes ratio. Total B and T cells decreased and Treg-to-CD8+ ratio increased. Functionality of T lymphocytes were not affected by any of the 3-fractionation schedules. Interestingly, SBRT significantly up-regulates the expression of V-domain immunoglobulin suppressor of T-cell activation (VISTA) in CD8+ T cells in the absence of other IRs. Our results indicate the relevance of systematic immunomonitoring during RT to identify novel immune-related target to design trials of combined radio-immunotherapy as a promising strategy in the clinical management of PCa.

A Systematic Review on the Impact of Hypofractionated and Stereotactic Radiotherapy on Immune Cell Subpopulations in Cancer Patients.

We investigated how hypofractionated radiotherapy (HFRT) and stereotactic body radiotherapy (SBRT) may impact immune cells in different type of tumors. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed, Embase and Cochrane databases were searched. Overall, 11 studies met the inclusion criteria and were eligible for the present analysis. Both HFRT and SBRT have different impact on lymphocyte subpopulations, confirming their immunomodulatory effect which may have a crucial role in future combined treatment with new emergent therapies such as immunotherapy. Further studies are needed to shed more light on this emerging topic to ultimately improve patient care, treatment and clinical benefits for cancer patients.

A choice experiment for testing the energy-efficiency mortgage as a tool for promoting sustainable finance.

The challenges currently facing the EU in the energy sector include increasing import dependence, limited diversification, high and volatile energy prices, decarbonization, and slow progress in energy efficiency. EU energy policy has provided a wide range of measures to achieve an integrated energy market and sustainability of the building sector. Various incentives and financial instruments have been promoted and financed by governments to help consumers in energy retrofit processes. These include direct investments and fiscal, financial, and market instruments. Public measures have been widely studied but private initiatives have not. In this study, the energy-efficiency mortgage (EEM) is investigated as a credit scheme to attract young people to a real estate market for sustainable buildings, characterized by high sale prices. A choice experiment (CE) was modelled to investigate the preferences of potential young buyers of a new home. The results of this exploratory survey showed an appreciation of the purchase of new A-rated properties according to the Energy Performance Certificate, compared to those that need to be retrofitted or not retrofitted. Consumers like the option of a home energy efficiency renovation being fully managed by a third party (i.e., following the one-stop shop model). The key appeal of energy efficiency for consumers ranges from its ability to support better energy management, to better property value management. The EEM seems to be a promising tool to stimulate investments in energy efficiency and to promote the accessibility and affordability of housing in the sustainable housing market. The results of this study can help private financial institutions to propose appropriate credit plans, which limit the risk of default by the borrower. They can also help public incentive policymakers to propose complementary instruments to EEM. Supplementary Information: The online version contains supplementary material available at 10.1007/s12053-022-10035-y.

Scenario building model to support the resilience planning of winemaking regions: The case of the Douro territory (Portugal).

Today resilience paradigm is shared by both academic and political debates, and it is gradually being implemented into plans, programmes, and project's initiatives. In this context, wine regions, particularly those designated as UNESCO sites, show their robustness and vulnerabilities as Socio-Ecological Systems. The climate change impact is increasing the exposure of their aesthetic, cultural, economic, natural values to potential losses and therefore an effective response is required To build resilient strategies, Decision Makers are increasingly considering multidimensional models in planning and assessment processes. This paper continues a research work that develops an integrated evaluation framework constituted by Multicriteria Decision Analysis to calculate a Territorial Resilience Index, a dynamical model to predict future ecological scenarios and scenario building to define a resilient strategy for the Douro territory (Portugal). This paper focuses on scenario building which uses specific tools such as Social Network Analysis to identify and investigate the relationships between real actors and stakeholders, Wilson matrix to assess the degree of uncertainty and relevance of the strategies identified by a panel of specialists, and consistency matrix to evaluate the strategies consistency in achieving the Sustainable Development Goals and UNESCO requirements. The obtained protocol of guidelines and recommendations can support Decision Makers in the design of sustainable and resilient transformation, thereby assisting in the preservation of the UNESCO site.

A prospective study assessing the pattern of response of local disease at DCE-MRI after salvage radiotherapy for prostate cancer.

Background: To assess the pattern of response of presumed local lesions at dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) after salvage radiotherapy (sRT). Methods: This is a prospective study conducted at a single Institution accruing patients with one or more local failures at DCE-MRI after radical prostatectomy between August 2017 and June 2020. Patients underwent exclusive sRT delivering 66-69 Gy and 73.5 Gy in 30 fractions to the whole prostatic fossa and to the local failure(s) seen at DCE-MRI, respectively.Patients were offered DCE-MRI at 3 months intervals after sRT until complete disappearance (CR) of the lesion(s) or up to a maximum of 4 revaluations. Results: 62 patients with 72 nodules were enrolled. All patients underwent the 1st revaluation, and 33 patients (53.2%) showed a CR. The median time to CR was 4.7 months. Four patients did not undergo further testing before achieving a CR and even considering these patients as no responses, the vast majority (87.1%, 95%CI: 78.5-94.4%) of lesions would have completely disappeared by 12 months from the end of sRT.The volume of the lesion at pre-sRT DCE-MRI was an independent predictor of CR at the 1st revaluation (OR: 0.076, 95%CI: 0.009-0.667; p = 0.020) along with time elapsed from sRT (OR: 3.399, 95% CI: 1.156-9.993, p = 0.026). Conclusions: The present study documents the complete disappearance of the vast majority of local lesions after dose-escalated sRT though this requires several months after sRT; timing of CR is at least in part predictable based on the volume of the lesion.Trial registration: Clinicaltrials.gov NCT04703543, registered July 15 2020, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04703543.

A systematic review and meta-analysis on non-metastatic castration resistant prostate cancer: The radiation oncologist's perspective.

Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic option is androgen deprivation: despite initial response rates, a progression to a state of castration resistance is observed in most of the patients. In the present article, we conducted a systematic review and meta-analysis of all clinical trials assessing treatment for nmCRPC with next-generation androgen receptor inhibitors. We performed a review and meta-analysis of phase III randomized controlled trials comparing new agents (apalutamide, enzalutamide, darolutamide) with placebo as control arm, in the setting of nmCRPC. Patients treated with next-generation ARIs had a 26% reduction in the risk of death compared with placebo; compared with other ARIs, darolutamide had the lowest rate of grade 3 and 4 AEs and the lowest therapy discontinuation rate due to any grade AEs. This meta-analysis shows that treatment with new ARIs is safe and significantly reduces the risk of death and of metastasis onset in nmCRPC patients. Under way studies on new biomarkers such as genomic classifiers will probably allow the stratification in more specific subsets of disease. New imaging modalities such as PSMA-PET have shown greater sensibility and specificity than conventional imaging in metastases detection. All patients were randomized in a 2:1 fashion, with a total of 2,694 who underwent next-generation ARIs (806 apalutamide, 955 darolutamide, 933 enzalutamide) and 1,423 in the placebo arm.

A decision support system for territorial resilience assessment and planning: An application to the Douro Valley (Portugal).

This paper aims to assess the territorial resilience of a socio-ecological system through an innovative integrated evaluation framework to aid the decision-making process in the planning of transformation scenarios. This framework employs a set of resilience indicators through a Multicriteria Decision Analysis (MCDA) coupled with a Lotka-Volterra mathematical model of cooperative type. The set of indicators aims to calculate a composite index of Territorial Resilience (TRI), whereas the mathematical model is an extension of an existing model, aimed to predict possible long-time scenarios. The proposed operational framework for rural and vineyard landscapes aims to bridge the existing gap between territorial resilience theory and practice, with an innovative Decision Support System able to assist Decision Makers and territory planners in the planning and management of resilient territorial systems. This integrated evaluation framework is applied to a famous wine region in Portugal, the Douro Valley, where Port-wine grows. Such framework, especially in a context of adaptive governance, proves to be a suitable support in the field of landscape and urban planning to evaluate the dynamics of socio-ecological systems and to envision long-term policies and actions.

The Italian Association of Radiotherapy and Oncology Recommendation for Breast Tumor Recurrence: Grades of Recommendation, Assessment, Development and Evaluation Criteria.

Salvage mastectomy is currently considered the standard of care for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and postoperative radiotherapy (RT). Alternative treatment options for these patients, such as a second BCS followed by repeated RT, have been suggested. The panel of the Italian Association of Radiotherapy and Clinical Oncology developed clinical recommendations for second BCS followed by re-irradiation over mastectomy alone for women with IBTR using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the evidence to decision framework. The following outcomes were identified by the panel: locoregional control, metastasis-free survival, overall survival, and cancer-specific survival; acute and late toxicity, specific late toxicity, second locoregional tumor, and death related to treatment. An Embase and PubMed literature search was performed by two independent authors. Five retrospective observational studies were eligible for inclusion in the present analysis. According to the reports in the literature and our analysis, the advantages of second quadrantectomy and re-irradiation (re-QUART) outweigh its side effects, with overall good rates of survival and adequate toxicity without increasing costs. Given the very low level of evidence, the panel stated that a second BCS plus re-irradiation can be considered as an alternative to salvage mastectomy for selected patients with IBTR.

A Prospective Study Assessing the Post-Prostatectomy Detection Rate of a Presumed Local Failure at mpMR with Either 64CuCl2 or 64CuPSMA PET/CT.

BACKGROUND: We aimed assess the detection rate (DR) of positron emission tomography/computed tomography with two novel tracers in patients referred for salvage radiotherapy (sRT) with a presumed local recurrence at multiparametric magnetic resonance (mpMR) after radical prostatectomy (RP). METHODS: The present prospective study was conducted at a single institution between August 2017 and June 2020. Eligibility criteria were undetectable PSA after RP; subsequent biochemical recurrence (two consecutive PSA rises to 0.2 ng/mL or greater); a presumed local failure at mpMR; no distant metastases at 18F-fluorocholine PET/CT (CH/PET); no previous history of androgen deprivation therapy. Patients were offered both 64CuCl2 PET/CT (CU/PET) and 64Cu-PSMA PET/CT (PSMA/PET) before sRT. After image co-registration, PET findings were compared to mpMR ones in terms of DR and independent predictors of DR investigated at logistic regression. RESULTS: A total of 62 patients with 72 nodules at mpMR were accrued. Compared to mpMR (DR = 100%, 95%CI: 94.9-100%), DRs were 47.2% (95%CI: 36.1-58.6%) and 54.4% (95%CI: 42.7-65.7%) for CU/PET and PSMA/PET, respectively (p < 0.001 for both). Both experimental PET/CT performed particularly poorly at PSA levels consistent with early sRT. CONCLUSIONS: The two novel radiotracers are inferior to mpMR in restaging the prostatic fossa for sRT planning purposes, particularly in the context of early salvage radiotherapy.

Electromagnetic Transponder Localization and Real-Time Tracking for Prostate Cancer Radiation Therapy: Clinical Impact of Metallic Hip Prostheses.

PURPOSE: Our purpose was to assess the ability of electromagnetic transponders (EMTs) to localize and track movements in patients with prostate cancer (PCa) with metallic hip prostheses (MHPs) treated with curative radiation therapy (RT). METHODS AND MATERIALS: Data sets of 8 PCa patients with MHPs (3 bilateral and 5 unilateral) treated between 2016 and 2018 with RT and EMT tracking were retrospectively assessed. The distances between the 3 EMTs (apex to left, left to right, right to apex) and the isocenter were calculated both on planning computed tomography (CT) and cone beam CT (CBCT) at the first treatment fraction and compared with data reported by Calypso. EMT position and treatment interruptions triggered by Calypso were analyzed for all evaluable treatment fractions (n = 120). Localization accuracy was quantified by recording the geometric residual value (expected limit ≤0.2 cm) at the RT setup. RESULTS: The Calypso system was able to localize and track prostate position without any detectable interference from MHP. For every treatment fraction, the agreement between the CBCT images and Calypso guidance was optimal, with EMTs always within the defined tolerance (ie, CT-Calypso or CBCT-Calypso measured differences in inter-EMT distances within 0.3 cm). EMT to isocenter distances measured by Calypso reproduced CT data and were confirmed on CBCT scans. During RT, the EMT centroid exceeded the threshold 24 times (20% of all fractions): 5 times in the left-right, 15 times in the anteroposterior, and 4 times in the superoinferior directions. The largest motions recorded were in the anteroposterior axis: 0.6 cm anteriorly and 0.5 cm posteriorly in patients with unilateral and bilateral MHP, respectively. CONCLUSIONS: Our study represents the first clinical experience assessing the localization and tracking accuracy of Calypso EMTs during curative RT of patients with PCa with unilateral or bilateral MHP.