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Purpose: To test any-cause discontinuation and ISUP GG upgrading rates during Active Surveillance (AS) in patients that underwent previous negative biopsies (PNBs) before prostate cancer (PCa) diagnosis vs. biopsy naive patients. Methods: Retrospective analysis of 961 AS patients (2008–2020). Three definitions of PNBs were used: (1) PNBs status (biopsy naïve vs. PNBs); (2) number of PNBs (0 vs. 1 vs. ≥ 2); (3) histology at last PNB (no vs. negative vs. HGPIN/ASAP). Kaplan–Meier plots and multivariable Cox models tested any-cause and ISUP GG upgrading discontinuation rates. Results: Overall, 760 (79.1%) vs. 201 (20.9%) patients were biopsy naïve vs. PNBs. Specifically, 760 (79.1%) vs. 138 (14.4%) vs. 63 (6.5%) patients had 0 vs. 1 vs. ≥ 2 PNBs. Last, 760 (79.1%) vs. 134 (13.9%) vs. 67 (7%) patients had no vs. negative PNB vs. HGPIN/ASAP. PNBs were not associated with any-cause discontinuation rates. Conversely, PNBs were associated with lower rates of ISUP GG upgrading: (1) PNBs vs. biopsy naïve (HR:0.6, p = 0.04); (2) 1 vs. 0 PNBs (HR:0.6, p = 0.1) and 2 vs. 0 PNBs, (HR:0.5, p = 0.1); (3) negative PNB vs. biopsy naïve (HR:0.7, p = 0.3) and HGPIN/ASAP vs. biopsy naïve (HR:0.4, p = 0.04). However, last PNB ≤ 18 months (HR:0.4, p = 0.02), but not last PNB > 18 months (HR:0.8, p = 0.5) were associated with lower rates of ISUP GG upgrading. Conclusion: PNBs status is associated with lower rates of ISUP GG upgrading during AS for PCa. The number of PNBs and time from last PNB to PCa diagnosis (≤ 18 months) appear also to be critical for patient selection. [ABSTRACT FROM AUTHOR]

As part of the AIRC IG-13218 (NCT01913717), we analyzed data from patients with low- and intermediate-risk prostate cancer treated with extreme hypofractionated radiotherapy (RT) and simultaneous boost to the intraprostatic lesion. The aim of the study is to identify clinically meaningful information through the analysis of validated questionnaires testing gastrointestinal (GI) and genitourinary (GU) RT-related toxicity and their impact on quality of life (QoL). At the end of RT treatment, clinical assessment and prostate-specific antigen (PSA) measurements were performed every 3 months for at least 2 years and GI and GU toxicities were evaluated contextually. QoL of enrolled patients was assessed by International Prostate Symptoms score (IPSS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), EORTC QLQ prostate specific (QLQ-PR25), and sexual activity by International Index of Erectile Function (IIEF-5). Patients' score changes were calculated at the end of RT, at one month after RT and at 12 and 24 months. Sixty-five prospectively enrolled patients were analyzed. Extensive analysis of different QoL assessments showed that patients' tolerance was satisfactory across all the considered time points, with no statistically significant change of QoL from baseline compared to that before RT. Overall survival and biochemical progression-free survival at 2-years were of 98% and 97%, respectively. Despite the toxicity of extreme hypofractionation was low and tumor control was encouraging, a longer follow-up is necessary to confirm our findings. The increasing dose to the dominant intraprostatic lesion does not worsen the RT toxicity and consequently does not affect patients' QoL, thus questioning the possibility of an even more escalated treatment. [ABSTRACT FROM AUTHOR]

Unfortunately, the denomination of the IEO was incorrectly published in the affiliation of this original [ABSTRACT FROM AUTHOR]

The aim of the study is to evaluate the scientific interest, the collaboration patterns and the emerging trends regarding HPV+ OPSCC diagnosis and treatment. A cross-sectional bibliometric analysis of articles reporting on HPV+ OPSCC within Scopus database was performed and all documents published up to December 31th, 2022 were eligible for analysis. Outcomes included the exploration of key characteristics (number of manuscripts published per year, growth rate, top productive countries, most highly cited papers, and the most well-represented journals), collaboration parameters (international collaboration ratio and networks, co-occurrence networks), keywords analysis (trend topics, factorial analysis). A total of 5200 documents were found, published from March, 1987 to December, 2022. The number of publications increased annually with an average growth rate of 19.94%, reaching a peak of 680 documents published in 2021. The 10 most cited documents (range 1105–4645) were published from 2000 to 2012. The keywords factorial analysis revealed two main clusters: one on epidemiology, diagnosis, prevention and association with other HPV tumors; the other one about the therapeutic options. According to the frequency of keywords, new items are emerging in the last three years regarding the application of Artifical Intelligence (machine learning and radiomics) and the diagnostic biomarkers (circulating tumor DNA). This bibliometric analysis highlights the importance of research efforts in prevention, diagnostics, and treatment strategies for this disease. Given the urgency of optimizing treatment and improving clinical outcomes, further clinical trials are needed to bridge unaddressed gaps in the management of HPV+ OPSCC patients. • Increasing number of publications on HPV+ OPSCC since 2007 with average annual growth rate of 19.94%. • International collaborations are a prominent feature in HPV+ OPSCC research. • Recent trends in HPV+ OPSCC research include artificial intelligence (AI) and ctDNA. [ABSTRACT FROM AUTHOR]

Purpose: To test discontinuation rates during Active Surveillance (AS) in patients diagnosed with incidental prostate cancers (IPCa) vs. tumors diagnosed at prostate biopsies (BxPCa). Methods: Retrospective single center analysis of 961 vs. 121 BxPCa vs. IPCa patients (2008–2020). Kaplan–Meier plots and multivariable Cox regression models tested four different outcomes: (1) any-cause discontinuation; (2) discontinuation due to ISUP GG upgrading; (3) biopsy discontinuation due to ISUP GG upgrading or > 3 positive cores; (4) biopsy discontinuation or suspicious extraprostatic extension at surveillance mpMRI. Then, multivariable logistic regression models tested rates of clinically significant PCa (csPCa) (ISUP GG ≥ 3 or pT ≥ 3a or pN1) after radical prostatectomy (RP). Results: Median time follow-up was 35 (19–64) months. IPCa patients were at lower risk of any-cause (3-year survival: 79.3 vs. 66%; HR: 0.5, p = 0.001) and biopsy/MRI AS discontinuation (3-year survival: 82.3 vs. 72.7%; HR: 0.5, p = 0.001), compared to BxPCa patients. Conversely, IPCa patients exhibited same rates of biopsy discontinuation and ISUP GG upgrading over time, relative to BxPCa. In multivariable logistic regression models, IPCa patients were associated with higher rates of csPCa at RP (OR: 1.4, p = 0.03), relative to their BxPCa counterparts. Conclusion: AS represents a safe management strategy for IPCa. Compared to BxPCa, IPCa patients are less prone to experience any-cause and biopsy/MRI AS discontinuation. However, the two mentioned groups present similar rates of biopsy discontinuation and ISUP GG upgrading over time. In consequence, tailored AS protocols with scheduled repeated surveillance biopsies should be offered to all newly diagnosed IPCa patients. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion To test the performance of ex vivo fluorescence confocal microscopy (FCM; Vivascope 2500M‐G4), as compared to intra‐operative frozen section (IFS) analysis, to evaluate surgical margins during robot‐assisted radical prostatectomy (RARP), with final pathology as the reference standard.Overall, 54 margins in 45 patients treated with RARP were analysed with: (1) ex vivo FCM; (2) IFS analysis; and (3) final pathology. FCM margins were evaluated by two different pathologists (experienced [M.I.: 10 years] vs highly experienced [G.R.: >30 years]) as strongly negative, probably negative, doubtful, probably positive, or strongly positive. First, inter‐observer agreement (Cohen's κ) between pathologists was tested. Second, we reported the sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV) of ex vivo FCM. Finally, agreement between ex vivo FCM and IFS analysis (Cohen's κ) was reported. For all analyses, four combinations of FCM results were evaluated.At ex vivo FCM, the inter‐observer agreement between pathologists ranged from moderate (κ = 0.74) to almost perfect (κ = 0.90), according to the four categories of results. Indeed, at ex vivo FCM, the highly experienced pathologist reached the best balance between sensitivity (70.5%) specificity (91.8%), PPV (80.0%) and NPV (87.1%). Conversely, on IFS analysis, the sensitivity, specificity, PPV and NPV were, respectively, 88.2% vs 100% vs 100% vs 94.8%. The agreement between the ex vivo FCM and IFS analyses ranged from moderate (κ = 0.62) to strong (κ = 0.86), according to the four categories of results.Evaluation of prostate margins at ex vivo FCM appears to be feasible and reliable. The agreement between readers encourages its widespread use in daily practice. Nevertheless, as of today, the performance of FCM seems to be sub‐par when compared to the established standard of care (IFS analysis). [ABSTRACT FROM AUTHOR]

Historically, non-seminomatous germ cell tumor (NSGCT) has been considered a radio-resistant disease, excluding radiotherapy (RT) from curative strategies. However, case series exploring the use of radiation treatment in this setting are often outdated, and prospective ongoing studies testing new radiotherapeutic approaches in NSGCT are lacking. Considering that tremendous advances in radiotherapy technology have enabled improved precision in RT delivery as well as dose escalation while decreasing treatment-related morbidity, we overviewed the currently available literature to explore the radiobiological basis, the technical issues, and potential strategies for implementation of RT in the management of this clinical entity. The purpose of the present overview is to provide insight for future research in this unexplored scenario. In summary, the biological rationale for RT use and potential implementation with systemic therapies exist, especially considering the advantage of new technologies, which were unavailable in the era of early literature reports. The NSGCT radioresistance paradigm could be based only on the fact that effective treatment schedules were simply undeliverable with older RT techniques due to toxicity issues, but the availability of actual techniques may prompt further exploration to offer treatment alternatives to these patients. Ongoing trials on this issue are lacking, but potential areas of research are platinum-refractory disease and consolidation therapy for residual masses after PST. [ABSTRACT FROM AUTHOR]

Purpose: To compare clinical outcomes and toxicities of 2 radiation therapy (RT) schemes for localized prostate cancer (PCa): extreme hypofractionation (EH; fractions of 6.5-7 Gy to a total dose of 32.5-35 Gy) and the moderate hypofractionation (MH; 26 fractions of 2.7 Gy to a total dose of 70.2 Gy). A propensity score method was used to compare the EH-RT and MH-RT groups.Methods and Materials: Our analysis included a total of 421 patients divided in 2 groups: 227 treated with MH-RT and 194 treated with EH-RT (43 and 30 months median follow-up, respectively). Propensity matching created comparable cohorts. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. Multivariate proportional hazard Cox models were used to compare the 2 groups, mainly for gastrointestinal and genitourinary toxicity and secondarily for clinical progression-free survival, biochemical progression-free survival, and overall survival.Results: Considering the whole population, acute genitourinary and gastrointestinal greater than grade 1 was significantly more frequent in the whole MH-RT group (P < .001 and P < .002, respectively). A borderline significantly greater late genitourinary was confirmed with the multivariate analysis (P = .07). Concerning tumor outcome, no statistically significant differences were observed. After propensity score matching, 226 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups.Conclusions: EH-RT yields a decreased risk of acute or late toxicities compared with MH-RT, and oncologic outcomes were comparable. Our data indicate that EH-RT might be considered as a treatment modality of choice for select patients with PCa. [ABSTRACT FROM AUTHOR]

Ultra-hypofractionated radiotherapy (RT) is given over a shorter time with larger doses with respect to conventional fractionation in patients with localized prostate cancer (PCa). The use of hypofractionation is supported both from the radiobiological point of view (the low α/β-ratio in PCa and dose escalation) and from the rising number of clinical evidences. The aim of this study is to review our data regarding oncological outcomes, namely biochemical progression-free survival (b-PFS) and clinical progression-free survival (c-PFS), acute and long-term toxicities in patients treated with a ultra-hypofractionated RT. A series of 194 patients with clinically localized PCa treated primarily with ultra-hypofractionated RT using image-guided intensity modulated RT (IG-IMRT) at our Institute from 2012 to 2015 was included in this analysis. According to NCCN risk group classification, 65 (33.5%) patients were low risk, 101 (52.1%) intermediate risk, and 28 (14.4%) high risk. Androgen deprivation therapy (ADT) was given to 61 patients (31.4%). A 169 patients (87.1%) received 35 Gy in 5 fractions, while 25 patients (13%) received 32.5 Gy in 5 fractions (usually given in patients with comorbidity). The median duration of the treatment was 10 days (IQR 9-12). Biochemical relapse was defined as a rise of prostate specific antigen (PSA) > 2 ng/ml above nadir. b-PFS, c-PFS, and freedom from gastro-intestinal (GI) and genito-urinary (GU) toxicity curves were calculated by the Kaplan-Meier method. Log-rank test and multivariate Cox models were used to investigate the role RT dose and heterogeneity by NCCN risk groups adjusting for prognostic factors. Data on acute and late term toxicities were collected according to RTOG/EORTC grading system. With a median follow-up of 30 months, 17 patients experienced PSA failure (9%). The 3-year b-PFS was 87% for all patients and rates stratified for the NCCN risk were 94, 82, and 66% for low-, intermediate-, and high-risk groups, respectively. Log-rank tests indicate that biochemical progression was significantly greater for patients with initial PSA (iPSA) greater than 7 ng/ml (P = 0.04), high- and intermediate-risk groups (P = 0.002), low total dose (P = 0.02) and Gleason score (GS) equal or greater than 7 (P = 0.04). No statistically significant association was found with T stage nor ADT. In multivariate analyses, total dose (P = 0.03) and risk groups (P = 0.03) remained significantly associated with recurrence. Acute and late GI and GU toxicity were acceptable. The toxicity of ultra-hypofractionated IG-IMRT in a large clinical cohort of PCa patients was tolerable and confirmed that this treatment is safe and offers excellent tumor control. Moreover, the hypofractionated RT allows to deliver the whole RT over 10 days with a sensible impact in patients' quality of life and potential overall health system and social benefits. [ABSTRACT FROM AUTHOR]

To evaluate outcome in patients treated with stereotactic body radiotherapy (SBRT) on bone oligometastases from castration-sensitive prostate cancer after primary treatment. We retrospectively collected data of patients with less than five lesions at time of SBRT and hormone-naïve disease at the first extra-regional localization, treated between 03/2012 and 11/2016. Prostate-specific antigen (PSA) was measured every 3 months after SBRT. Imaging was performed in case of progression. Survival analysis was performed with Kaplan-Meier (log-rank test) approach. Fifty-five patients were treated on 77 bone oligometastases. Median age, initial PSA and pre-SBRT PSA were 72 years, 9.12 and 3.5 ng/mL, respectively. Twenty-five patients (45%) received SBRT alone while the remaining 30 patients (55%) received concomitant ADT. Median follow-up was 24.6 months (range 3.0-67.2 months). No acute or late toxicity of grade > 1 was reported. Clinical progression was observed in 38 (69%) patients. 1-year biochemical progression-free survival (b-PFS), clinical progression-free survival (c-PFS), prostate-specific survival (PCSS) and local control (LC) rates were 51, 56, 100 and 83%, respectively. Comparing patients treated with SBRT alone and with concomitant ADT, no significant differences were found for those outcomes. SBRT is safe and allows high 1-year LC rate (83%) with low toxicity profile. No significant improvement in outcomes was registered with the addition of ADT to SBRT. [ABSTRACT FROM AUTHOR]

Simple Summary: The therapeutic potential of proton therapy (PT) was first recognized in 1946 by Robert Wilson, and nowadays, over 100 proton centers are in operation worldwide, and more than 60 are under construction or planned. Bibliometrics allows us to assess the growth and development of the field and provides an overview of the most relevant sources, authors, and institutions in the chosen field. Additionally, keyword analysis can be performed to provide details that could aid in identifying research trends and hot topics. Indeed, bibliometrics allows for identifying the basic and dominant themes and trends, as well as those emerging or declining. The aim of this study is to provide a comprehensive bibliometric analysis of the current status and trends in scientific literature in the PT field. The analysis will give an overview of past scientific production and, most importantly, provide a useful point of view on the future directions of the research activities. Background: The therapeutic potential of proton therapy (PT) was first recognized in 1946 by Robert Wilson, and nowadays, over 100 proton centers are in operation worldwide, and more than 60 are under construction or planned. Bibliometric data can be used to perform a structured analysis of large amounts of scientific data to provide new insights, e.g., to assess the growth and development of the field and to identify research trends and hot topics. The aim of this study is to provide a comprehensive bibliometric analysis of the current status and trends in scientific literature in the PT field. Methods: The literature on PT until the 31st December 2022 in the Scopus database was searched, including the following keywords: proton AND radiotherapy AND cancer/tumor in title, abstract, and/or keywords. The open-source R Studio's Bibliometrix package and Biblioshiny software (version 2.0) were used to perform the analysis. Results: A total of 7335 documents, mainly articles (n = 4794, 65%) and reviews (n = 1527, 21%), were collected from 1946 to 2022 from 1054 sources and 21,696 authors. Of these, roughly 84% (n = 6167) were produced in the last 15 years (2008–2022), in which the mean annual growth rate was 13%. Considering the corresponding author's country, 79 countries contributed to the literature; the USA was the top contributor, with 2765 (38%) documents, of whom 84% were single-country publications (SCP), followed by Germany and Japan, with 535 and 531 documents of whom 66% and 93% were SCP. Considering the themes subanalysis (2002–2022), a total of 7192 documents were analyzed; among all keywords used by authors, the top three were radiotherapy (n = 1394, 21% of documents), intensity-modulated radiotherapy (n = 301, 5%), and prostate cancer (n = 301, 5%). Among disease types, prostate cancer is followed by chordoma, head and neck, and breast cancer. The change in trend themes demonstrated the fast evolution of hotspots in PT; among the most recent trends, the appearance of flash, radiomics, relative biological effectiveness (RBE), and linear energy transfer (LET) deserve to be highlighted. Conclusions: The results of the present bibliometric analysis showed that PT is an active and rapidly increasing field of research. Themes of the published works encompass the main aspects of its application in clinical practice, such as the comparison with the actual photon-based standard of care technique and the continuing technological advances. This analysis gives an overview of past scientific production and, most importantly, provides a useful point of view on the future directions of the research activities. [ABSTRACT FROM AUTHOR]

In this technical development report, we present the strategic placement of fiducial markers within the prostate under the guidance of computed tomography (CT) and electromagnetic navigation (EMN) for the delivery of ultra-hypofractionated cyberknife (CK) therapy in a patient with localized prostate cancer (PCa) who had previously undergone chemo-radiotherapy for rectal cancer and subsequent abdominoperineal resection due to local recurrence. The patient was positioned in a prone position with a pillow under the pelvis to facilitate access, and an electromagnetic fiducial marker was placed on the patient's skin to establish a stable position. CT scans were performed to plan the procedure, mark virtual points, and simulate the needle trajectory using the navigation system. Local anesthesia was administered, and a 21G needle was used to place the fiducial markers according to the navigation system information. A confirmatory CT scan was obtained to ensure proper positioning. The implantation procedure was safe, without any acute side effects such as pain, hematuria, dysuria, or hematospermia. Our report highlights the ability to use EMN systems to virtually navigate within a pre-acquired imaging dataset in the interventional room, allowing for non-conventional approaches and potentially revolutionizing fiducial marker positioning, offering new perspectives for PCa treatment in selected cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Automatic segmentation of organs and other regions of interest is a promising approach for reducing the workload of doctors in radiotherapeutic planning, but it can be hard for doctors and researchers to keep up with current developments. This review evaluates 807 papers and reveals trends, commonalities, and gaps in the existing corpus. A set of recommendations for conducting effective segmentation studies is also provided. This review provides a formal overview of current automatic segmentation studies that use deep learning in radiotherapy. It covers 807 published papers and includes multiple cancer sites, image types (CT/MRI/PET), and segmentation methods. We collect key statistics about the papers to uncover commonalities, trends, and methods, and identify areas where more research might be needed. Moreover, we analyzed the corpus by posing explicit questions aimed at providing high-quality and actionable insights, including: "What should researchers think about when starting a segmentation study?", "How can research practices in medical image segmentation be improved?", "What is missing from the current corpus?", and more. This allowed us to provide practical guidelines on how to conduct a good segmentation study in today's competitive environment that will be useful for future research within the field, regardless of the specific radiotherapeutic subfield. To aid in our analysis, we used the large language model ChatGPT to condense information. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The aim of this study is to test whether radiomic and blood-derived biomarkers are good candidates for refining the prognostic stratification in OPSCC. The results show that the integration of clinical, immunological, and computed tomography-derived features generally yields an improvement, regardless of the HPV status, in the prognostic stratification of OPSCC patients who are candidates for curative-intent radiotherapy. Specifically, we documented a significant role of the Lymphocyte-to-Monocyte Ratio (LMR) in this population, which has been scarcely investigated in OPSCC, as well as the detrimental effects of lymphopenia and anemia. Results are promising, and model performances compare favorably with available radiomic scores in the same setting. Further investigations on our findings are warranted to validate the results and include a more in-depth study of the prognostic role of the LMR in OPSCC. Future analyses of this dataset are planned to provide a more complete overview of the tumor-immune system interplay. Aims: To assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT. Methods: Consecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models' performance was compared by the C-index. Results: One hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52–66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5–7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80–0.84] for OS and 0.77 [CI: 0.75–0.79] for LRPFS. Conclusions: Our results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • Using different platforms for radiomic extraction affects models' performance. • Variables' relevance is inconsistent among platforms. • MRI features are correlated to radiosurgery response in brain metastases from NSCLC. • Higher number of radiomic features does not necessarily imply better performance. Radiomics enables the mining of quantitative features from medical images. The influence of the radiomic feature extraction software on the final performance of models is still a poorly understood topic. This study aimed to investigate the ability of radiomic features extracted by two different radiomic platforms to predict clinical outcomes in patients treated with radiosurgery for brain metastases from non-small cell lung cancer. We developed models integrating pre-treatment magnetic resonance imaging (MRI)-derived radiomic features and clinical data. Pre-radiotherapy gadolinium enhanced axial T1-weighted MRI scans were used. MRI images were re-sampled, intensity-shifted, and histogram-matched before radiomic extraction by means of two different platforms (PyRadiomics and SOPHiA Radiomics). We adopted LASSO Cox regression models for multivariable analyses by creating radiomic, clinical, and combined models using three survival clinical endpoints (local control, distant progression, and overall survival). The statistical analysis was repeated 50 times with different random seeds and the median concordance index was used as performance metric of the models. We analysed 276 metastases from 148 patients. The use of the two platforms resulted in differences in both the quality and the number of extractable features. That led to mismatches in terms of end-to-end performance, statistical significance of radiomic scores, and clinical covariates found significant in combined models. This study shed new light on how extracting radiomic features from the same images using two different platforms could yield several discrepancies. That may lead to acute consequences on drawing conclusions, comparing results across the literature, and translating radiomics into clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to compare effectiveness and cost profile in non-small-cell lung cancer (NSCLC) patients harboring synchronous brain metastases (BMs) who received non-chemo first-line systemic therapy with or without advanced radiotherapy (aRT). A total of 177 lung cancer patients, of whom 58 were treated with systemic treatment (either TKIs or pembrolizumab) plus aRT (STRT) and 119 with systemic treatment alone, were selected. The addition of aRT to systemic treatment was associated with a significantly better OS (p = 0.020) and PFS (p = 0.041) than systemic therapy alone. The incremental cost-effectiveness ratio (ICER) value indicated an average cost of €3792 for each month of survival after STRT and confirmed clinical effectiveness but higher healthcare costs. This real-world study suggests that upfront aRT in this setting represents a valid treatment strategy, boosting the efficacy of emerging drug classes with sustainable costs for the health service. Aim: Healthcare administrative databases represent a valuable source for real-life data analysis. The primary aim of this study is to compare effectiveness and cost profile in non-small-cell lung cancer (NSCLC) patients harboring synchronous brain metastases (BMs) who received non-chemo first-line systemic therapy with or without advanced radiotherapy (aRT). Methods: Diagnostic ICD-9-CM codes were used for identifying all patients with a new diagnosis of lung cancer between 2012 and 2019. Among these, patients who had started a first-line systemic treatment with either TKIs or pembrolizumab, alone or in combination with intensity-modulated or stereotactic RT, were selected. Clinical outcomes investigated included overall survival (OS), progression-free survival (PFS), and time-to-treatment failure (TTF). The cost outcome was defined as the average per capita cumulative healthcare direct costs of the treatment, including all inpatient and outpatient costs. Results: The final cohort included 177 patients, of whom 58 were treated with systemic treatment plus aRT (STRT) and 119 with systemic treatment alone. The addition of aRT to systemic treatment was associated with a significantly better OS (p = 0.020) and PFS (p = 0.041) than systemic therapy alone. The ICER (incremental cost-effectiveness ratio) value indicated an average cost of €3792 for each month of survival after STRT treatment and confirmed clinical effectiveness but higher healthcare costs. Conclusions: This real-world study suggests that upfront aRT for NCLSC patients with synchronous BMs represents a valid treatment strategy, boosting the efficacy of novel and emerging drug classes with sustainable costs for the health service. Translational relevance: The present real-world study reports that the use of upfront advanced radiotherapyaRT and new-generation systemic agents, such as TKIs and pembrolizumab, may have higher oncological control and an improved cost-effectiveness profile than the use of new-generation systemic agents alone in NCLSC patients with synchronous brain metastases. Acquired evidence can also be used to inform policymakers that adding advanced radiotherapy results is a sustainable cost for the health service. Since approximately 50% of patients do not meet RCT inclusion criteria, a significant proportion of them is receiving treatment that is not evidence-informed; therefore, these results warrant further studies to identify the best radiotherapy timing and possible dose escalation approaches to improving treatment efficacy in patient subgroups not typically represented in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Radiotherapy represents a highly targeted and efficient treatment choice in many cancer types, both with curative and palliative intents. Nevertheless, radioresistance, consisting in the adaptive response of the tumor to radiation-induced damage, represents a major clinical problem. A growing body of the literature suggests that mechanisms related to mitochondrial changes and metabolic remodeling might play a major role in radioresistance development. In this work, the main contributors to the acquired cellular radioresistance and their relation with mitochondrial changes in terms of reactive oxygen species, hypoxia, and epigenetic alterations have been discussed. We focused on recent findings pointing to a major role of mitochondria in response to radiotherapy, along with their implication in the mechanisms underlying radioresistance and radiosensitivity, and briefly summarized some of the recently proposed mitochondria-targeting strategies to overcome the radioresistant phenotype in cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Data regarding the survival effect of radical prostatectomy in patients with oligometastatic PC (OPC) are sparse and based on small series. Moreover, few studies compared radical prostatectomy with systemic treatment in an OPC setting. We compared multimodality treatment (MMT, defined as robot-assisted radical prostatectomy (RARP) with androgen deprivation therapy (ADT), with or without adjuvant radiotherapy (RT)) vs. ADT alone in oligometastatic prostate cancer (OPC) patients. MMT was associated with lower CSM, mCRPC and second-line therapy rates. A lower rate of treatment-related adverse events was recorded for the MMT group. Background: We compared multimodality treatment (MMT, defined as robot-assisted radical prostatectomy (RARP) with androgen deprivation therapy (ADT), with or without adjuvant radiotherapy (RT)) vs. ADT alone in oligometastatic prostate cancer (OPC) patients. Methods: From 2010 to 2018, we identified 74 patients affected by cM1a-b OPC (≤5 metastases). Kaplan–Meier (KM) plots depicted cancer-specific mortality (CSM), disease progression, metastatic castration-resistant PC (mCRPC), and time to second-line systemic therapy rates. Multivariable Cox regression models (MCRMs) focused on disease progression and mCRPC. Results: Forty (54.0%) MMT and thirty-four (46.0%) ADT patients were identified. On KM plots, higher CSM (5.9 vs. 37.1%; p = 0.02), mCRPC (24.0 vs. 62.5%; p < 0.01), and second-line systemic therapy (33.3 vs. 62.5%; p < 0.01) rates were recorded in the ADT group. No statistically significant difference was recorded for disease progression. ForMCRMs adjusted for the metastatic site and PSA, a higher mCRPC rate was recorded in the ADT group. No statistically significant difference was recorded for disease progression. Treatment-related adverse events occurred in 5 (12.5%) MMT vs. 15 (44.1%) ADT patients (p < 0.01). Conclusions: MMT was associated with lower CSM, mCRPC, and second-line therapy rates. A lower rate of treatment-related adverse events was recorded for the MMT group. [ABSTRACT FROM AUTHOR]

Background: Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m2/q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m2/q1.Methods: Patients were treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules.Results: Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule.Conclusions: 3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients. [ABSTRACT FROM AUTHOR]

We analyzed 400 patients who underwent prostate cancer surgery investigating apparent diffusion coefficient (ADC) values and magnetic resonance imaging features for predicting positive surgical margins (PSMs). ADC values, Prostate Imaging Reporting and Data System category, extracapsular extension score, site, and laterality were associated with PSMs; ADC performed well in PSM prediction; lower ADC values were present in patients with PSMs Purpose: To investigate the use of apparent diffusion coefficient (ADC) values and other MRI features for predicting positive surgical margins (PSMs) in patients undergoing radical prostatectomy. Materials and Methods: We retrospectively identified 400 consecutive patients who underwent surgery for prostate cancer between January 2015 and June 2016. ADC values of the index lesion and other preoperative magnetic resonance imaging features, including tumor site, laterality, level, Prostate Imaging Reporting and Data System category, European Society of Urogenital Radiology extracapsular extension score, and prostate volume, were assessed. Univariate and multivariable logistic regression were performed. Performance in predicting the occurrence of PSMs was measured using the area under the curve (AUC). AUC differences were evaluated with the DeLong method. The Youden index was calculated to identify the ADC threshold to best discriminate patients with PSMs. Results: Of the 400 patients, 105 (26.2%) had PSMs after radical prostatectomy. ADC values, Prostate Imaging Reporting and Data System category, extracapsular extension score, tumor site, and laterality were significantly associated with PSMs (P < .001) in univariate analysis. The AUC of the predictive model based on ADC alone was 68.2% (95% confidence interval, 62.2-74.2%) and did not significantly differ from the best multivariable predictive model which combined laterality, and site with ADC to attain an AUC of 70.0% (95% confidence interval, 64.2-75.8%; DeLong P = .318). The ADC threshold that maximized the Youden index was 960.3 µm 2/s. Conclusion: ADC values and preoperative magnetic resonance imaging features can help estimate the risk of PSMs after radical prostatectomy. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates (ADCs) represent a therapeutic class of agents designed to selectively deliver cytotoxic payloads to cancer cells. With the increasingly positioning of ADCs in the clinical practice, combinations with other treatment modalities, including radiation therapy (RT), will open new opportunities but also challenges. This review evaluates ADC-RT interactions, examining therapeutic synergies and potential caveats. ADC payloads can be radiosensitizing, enhancing cytotoxicity when used in combination with RT. Antigens targeted by ADCs can have various tissue expressions, resulting in possible off-target toxicities by tissue radiosensitization. Notably, the HER-2-directed ADC trastuzumab emtansine has appeared to increase the risk of radionecrosis when used concomitantly with brain RT, as glial cells can express HER2, too. Other possible organ-specific effects are discussed, such as pulmonary and cardiac toxicities. The lack of robust clinical data on the ADC-RT combination raises concerns regarding specific side effects and the ultimate trade-off of toxicity and safety of some combined approaches. Clinical studies are needed to assess ADC-RT combination safety and efficacy. [Display omitted] • Antibody drug-conjugated (ADC) may enhance cell death when combined with radiation. • Selected ADCs combined have shown to increase the risk of radionecrosis • Specific RT-toxicities are of major concern because they can add on known adverse effects of ADCs • Photoimmunotherapy offers opportunities, requiring exploration of its interaction [ABSTRACT FROM AUTHOR]

Objectives: Radiomic involves testing the associations of a large number of quantitative imaging features with clinical characteristics. Our aim was to extract a radiomic signature from axial T2-weighted (T2-W) magnetic resonance imaging (MRI) of the whole prostate able to predict oncological and radiological scores in prostate cancer (PCa). Methods: This study included 65 patients with localized PCa treated with radiotherapy (RT) between 2014 and 2018. For each patient, the T2-W MRI images were normalized with the histogram intensity scale standardization method. Features were extracted with the IBEX software. The association of each radiomic feature with risk class, T-stage, Gleason score (GS), extracapsular extension (ECE) score, and Prostate Imaging Reporting and Data System (PI-RADS v2) score was assessed by univariate and multivariate analysis. Results: Forty-nine out of 65 patients were eligible. Among the 1702 features extracted, 3 to 6 features with the highest predictive power were selected for each outcome. This analysis showed that texture features were the most predictive for GS, PI-RADS v2 score, and risk class; intensity features were highly associated with T-stage, ECE score, and risk class, with areas under the receiver operating characteristic curve (ROC AUC) ranging from 0.74 to 0.94. Conclusions: MRI-based radiomics is a promising tool for prediction of PCa characteristics. Although a significant association was found between the selected features and all the mentioned clinical/radiological scores, further validations on larger cohorts are needed before these findings can be applied in the clinical practice. Key Points: • A radiomic model was used to classify PCa aggressiveness. • Radiomic analysis was performed on T2-W magnetic resonance images of the whole prostate gland. • The most predictive features belong to the texture (57%) and intensity (43%) domains. [ABSTRACT FROM AUTHOR]

Highlights • Analysis of the outcome of 180 DCIS patients treated with intraoperative electrons. • The whole population showed high local relapse rate, increasing over time. • Suitable Group, according to ASTRO APBI, showed a 5-year local relapse rate of 11%. • Pathological characteristics were not sufficient to select low risk group. • Integration with biomolecular factors (ER/PgR and HER2 receptors) is needed. Abstract Aims To report the long-term outcome of a single institution series of pure ductal carcinoma in situ (DCIS) treated with accelerated partial irradiation using intraoperative electrons (IOERT). Methods From 2000 to 2010, 180 DCIS patients, treated with quadrantectomy and 21 Gy IOERT, were analyzed in terms of ipsilateral breast recurrences (IBRs) and survival outcomes by stratification in two subgroups. The low-risk group included patients who fulfilled the suitable definition according to American Society of Radiation Oncology (ASTRO) Guidelines (size ≤2.5 cm, grade 1–2 and surgical margins ≥3 mm) (Suitable), while the remaining ones formed the high-risk group (Non-Suitable). Results Eighty-four and 96 patients formed the Suitable and Non-Suitable groups, respectively. In the whole population, the cumulative incidence of IBR at 5, 7 and 10 years was 19%, 21%, and 25%, respectively. In the Suitable group, the cumulative incidence of IBR remained constant at 11% throughout the years, while in the Non-Suitable group increased from 26% at 5 years to 36% at 10 years (p < 0.0001). When hormonal positivity and HER2 absence of expression were added to the selection of the Suitable group, the cumulative incidence of IBR dropped and stabilized at 4% at 10 years. None died of breast cancer. In the whole population, 5-year and 10-year overall survival rate was 98% and 96.5%, respectively, without any difference between the two groups. Conclusions The overall and by group IBR rates were high and stricter criteria are required for acceptable local control for Suitable DCIS. Because of the concerns raised, IOERT should not be used in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Clinical development and use of novel systemic agents in combination with radiotherapy (RT) is at nowadays most advanced in the field of treatment of solid tumors. Although for many of these substances preclinical studies provide sufficient evidences on their principal capability to enhance radiation effects, the majority of them have not been investigated in even phase I clinical trials for safety in the context of RT. In clinical practice, unexpected acute and late side effects may emerge especially in combination with RT. As a matter of fact, despite combined modality treatment holds potential for enhancing the therapeutic ratio, some concerns are raised from the lack of high-quality clinical data to guide the care of patients who are treated with novel compounds in conjunction with RT. The aim of this review is to provide, from a radio-oncological point of view, an overview of the most advanced combined treatment concepts for solid tumors focusing on treatment toxicity. [ABSTRACT FROM AUTHOR]

Abstract Over the past century, technologic advances have promoted the evolution of radiation therapy into a precise treatment modality allowing for the maximal administration of dose to tumors while sparing normal tissues. In parallel with this technological maturation, the rapid expansion in understanding the basic biology and heterogeneity of cancer has led to the development of several compounds that target specific pathways. Many of them are in advanced steps of clinical development for combination treatments with radiotherapy, and can be incorporated into radiation oncology practice for a personalized approach to maximize the therapeutic gain. This review describes the rationale for combining novel agents with radiation, and provides an overview of the current landscape focused on treatment efficacy. [ABSTRACT FROM AUTHOR]

• Conditional survival models showed a direct relationship between event-free time and active surveillance (AS) permanence. • Even patients with worst disease achieve good survival probabilities after 5 years. • Intensify follow-up schemes in the first 2 years of AS. To determine risk categories for patients with prostate cancer (PCa) in active surveillance (AS) and to test the conditional survival (CS) that examined the effect of event-free survival since AS-entrance. From January 2012 to December 2020 we analyzed 606 patients with PCa enrolled in our AS program. Kaplan-Meier (KM) plots depicted AS-exit rate. Multivariable Cox regression models (MCRMs) tested for AS-exit rate independent predictors to determine risk categories. CS estimates were used to calculate overall AS-exit rate after event-free survival intervals of 1, 2, 3, and 5 years, and after stratification according to risk categories. At MCRMs PSAd ≥ 0.15 (HR: 1.43; P -value 0.04), PI-RADS 4-5 (HR: 2.56; P -value <0.001) and number of biopsy positive cores ≥ 2 (HR: 1.75; P -value <0.001) were independent predictors of AS-exit. These variables were used to determine risk categories: low-, intermediate- and high-risk. Overall, according to CS-analyses, 5-year AS-exit free rate increased from 59.7% at baseline, to 67.3%, 74.7%, and 89.4% in patients who remained in AS respectively ≥1, ≥2, ≥3 and ≥5 years. After stratification according to risk categories, in those patients who remained in AS ≥ 5 years, 5-year AS-exit free rates increased from 76.3% to 100% in patients with a low-risk, from 62.7% to 83.7% in patients with an intermediate-risk and from 42.3% to 87.5% in patients with a high-risk. CS models showed a direct relationship between event-free survival duration and subsequent AS permanence in overall PCa patients and after stratification according to risk categories. [ABSTRACT FROM AUTHOR]

18 F-fluorodeoxyglucose PET/CT ( 18 F-FDG-PET/CT) is widely applied in oncology for disease staging, assessment of therapy response, relapse diagnosis, follow-up and target volume delineation. In particular, it can detect early response during chemoradiotherapy (interim) because functional modifications usually precede morphological ones. This ability is crucial to the radiation oncologist for the management of patients, to avoid persisting with ineffective therapy − often leading toxicity − and to shift to potentially more effective alternatives. Interim 18 F FDG-PET imaging in rectal and cervical cancer, the main malignancies of the pelvic district, has been applied and a broad literature is available, although some results are discordant. This systematic review summarizes the application of 18 F FDG-PET/CT during the chemoradiotherapy of locally advanced pelvic malignancies in order to clarify its capability to predict response and prognosis and its potential role to tailor therapy, which seems to be validated in rectal cancer, whilst less conclusive in cervical cancer. [ABSTRACT FROM AUTHOR]

To provide a literature review on risk factors and strategies to prevent acute carotid blowout (CBO) syndrome in patients who underwent reirradiation (reRT) for recurrent head and neck (HN) malignancies. Inclusion criteria were: 1) CBO following reRT in the HN region, 2) description on patient-, tumor- or treatment-related risk factors, 3) clinical or radiological signs of threatened or impending CBO, and 4) CBO prevention strategies. Thirty-five studies were selected for the analysis from five hundred seventy-seven records. Results provided indications on clinical, radiological and dosimetric parameters possibly associated with higher risk of CBO. Endovascular procedures (artery occlusion and stenting) to prevent acute massive hemorrhage in high risk patients were discussed. Literature data are still scarce with a low level of evidence. Nevertheless, the present work provides a comprehensive review useful for clinicians as a multidisciplinary pragmatic tool in their clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To focus on the ecological footprint of radiotherapy (RT), on opportunities for sustainable practices, on future research directions., Methods: Different databases were interrogated using the following terms: Carbon Footprint, Sustainab*, Carbon Dioxide, Radiotherapy, and relative synonyms., Results: 931 records were retrieved; 15 reports were included in the review. Eight main thematic areas have been identified. Nine research works analyzed the environmental impact of photon-based external beam RT. Particle therapy was the subject of one work. Other thematic areas were brachytherapy, intra-operative RT, telemedicine, travel-related issues, and the impact of COVID-19., Conclusion: This review demonstrates the strong interest in identifying novel strategies for a more environmentally friendly RT and serves as a clarion call to unveil the environmental impact of carbon footprints entwined with radiation therapy. Future research should address current gaps to guide the transition towards greener practices, reducing the environmental footprint and maintaining high-quality care., Competing Interests: Declaration of Competing Interest Division of Radiotherapy IEO received research funding from AIRC (Italian Association for Cancer Research) and Fondazione IEO-CCM (Istituto Europeo di Oncologia-Centro Cardiologico Monzino) (all outside the current project). BAJF received speaker fees from Roche, Bayer, Janssen, Carl Zeiss, Ipsen, Accuray, Astellas, Elekta, IBA, Astra Zeneca (all outside the current project). IEO, the European Institute of Oncology IRCCS, was partially supported by institutional grants from Accuray Inc. and IBA (Ion Beam Applications, Louvain-la-Neuve, ‎Belgium). The sponsors did not play any role in the study design, collection, analysis and interpretation of data, nor in the writing of the manuscript, nor in the decision to submit the manuscript for publication. The remaining authors declare no conflicts of interest that are relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)