Muscle-invasive bladder cancer in elderly and frail people: Is hypofractionated radiotherapy a feasible approach when no other local options are available?

AIM: The study aims to report the feasibility and safety of palliative hypofractionated radiotherapy targeting macroscopic bladder tumors in a monocentric cohort of frail and elderly bladder cancer patients not eligible for curative treatments. METHODS: Patients who underwent hypofractionated radiotherapy to the gross disease or to the tumor bed after transurethral resection of bladder tumor from 2017 to 2021 at the European Institute of Oncology IRCCS, were retrospectively considered. Schedules of treatment were 30 and 25 Gy in 5 fractions (both every other day, and consecutive days). Treatment response was evaluated with radiological investigation and/or cystoscopy. Toxicity assessment was carried out according to RTOG/EORTC v2.0 criteria. RESULTS: A total of 16 patients were included in the study, of these 11 received hypofractionated radiotherapy on the macroscopic target volume and five on the tumor bed after transurethral resection of bladder tumor. No grade (G) >2 acute toxicities were described after treatment for both groups. Only one patient in the group receiving radiotherapy on the macroscopic disease reported G4 GU late toxicity. Ten patients had available follow-up status (median FU time 18 months), of them six had complete response, one had stable disease, and three had progression of disease. The overall response rate and disease control rate were 60% and 70%, respectively. CONCLUSION: Our preliminary data demonstrate that palliative hypofractionated radiotherapy for bladder cancer in a frail and elderly population is technically feasible, with an acceptable toxicity profile. These outcomes emphasize the potential of this approach in a non-radical setting and could help to provide more solid indications in this underrepresented setting of patients.

Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Photon vs proton hypofractionation in prostate cancer: A systematic review and meta-analysis.

BACKGROUND: High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa. METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies). RESULTS: A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes. CONCLUSION: The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT.

Can we predict pathology without surgery? Weighing the added value of multiparametric MRI and whole prostate radiomics in integrative machine learning models.

OBJECTIVE: To test the ability of high-performance machine learning (ML) models employing clinical, radiological, and radiomic variables to improve non-invasive prediction of the pathological status of prostate cancer (PCa) in a large, single-institution cohort. METHODS: Patients who underwent multiparametric MRI and prostatectomy in our institution in 2015-2018 were considered; a total of 949 patients were included. Gradient-boosted decision tree models were separately trained using clinical features alone and in combination with radiological reporting and/or prostate radiomic features to predict pathological T, pathological N, ISUP score, and their change from preclinical assessment. Model behavior was analyzed in terms of performance, feature importance, Shapley additive explanation (SHAP) values, and mean absolute error (MAE). The best model was compared against a naïve model mimicking clinical workflow. RESULTS: The model including all variables was the best performing (AUC values ranging from 0.73 to 0.96 for the six endpoints). Radiomic features brought a small yet measurable boost in performance, with the SHAP values indicating that their contribution can be critical to successful prediction of endpoints for individual patients. MAEs were lower for low-risk patients, suggesting that the models find them easier to classify. The best model outperformed (p ≤ 0.0001) clinical baseline, resulting in significantly fewer false negative predictions and overall was less prone to under-staging. CONCLUSIONS: Our results highlight the potential benefit of integrative ML models for pathological status prediction in PCa. Additional studies regarding clinical integration of such models can provide valuable information for personalizing therapy offering a tool to improve non-invasive prediction of pathological status. CLINICAL RELEVANCE STATEMENT: The best machine learning model was less prone to under-staging of the disease. The improved accuracy of our pathological prediction models could constitute an asset to the clinical workflow by providing clinicians with accurate pathological predictions prior to treatment. KEY POINTS: • Currently, the most common strategies for pre-surgical stratification of prostate cancer (PCa) patients have shown to have suboptimal performances. • The addition of radiological features to the clinical features gave a considerable boost in model performance. Our best model outperforms the naïve model, avoiding under-staging and resulting in a critical advantage in the clinic. •Machine learning models incorporating clinical, radiological, and radiomics features significantly improved accuracy of pathological prediction in prostate cancer, possibly constituting an asset to the clinical workflow.

Extreme-hypofractionated RT with concomitant boost to the DIL in PCa: a 5-year update on oncological and patient-reported outcomes for the phase II trial "GIVE ME FIVE".

AIM: The present work reports updated oncological results and patients-reported outcomes at 5 years of phase II trial "Short-term high precision RT for early prostate cancer with SIB to the dominant intraprostatic lesion (DIL) for patients with early-stage PCa". METHODS: Data from patients enrolled within AIRC IG-13218 (NCT01913717) trial were analyzed. Clinical and GU/GI toxicity assessment and PSA measurements were performed every 3 months for at least 2 years after RT end. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and IIEF-5. Patients' score changes were calculated at the end of RT and at 1, 12, and 60 months after RT. RESULTS: A total of 65 patients were included. At a median follow-up of 5 years, OS resulted 86%. Biochemical and clinical progression-free survival at 5 years were 95%. The median PSA at baseline was 6.07 ng/ml, while at last follow-up resulted 0.25 ng/ml. IPSS showed a statistically significant variation in urinary function from baseline (p = 0.002), with the most relevant deterioration 1 month after RT, with a recovery toward baseline at 12 months (p ≤ 0.0001). A numerical improvement in QoL according to the EORTC QLQ-C30 has been reported although not statistically significant. No change in sexual activity was recorded after RT. CONCLUSIONS: The study confirms that extreme hypofractionation with a DIL boost is safe and effective, with no severe effects on the QoL. The increasing dose to the DIL does not worsen the RT toxicity, thus opening the possibility of an even more escalated treatment.

Mapping the research landscape of HPV-positive oropharyngeal cancer: a bibliometric analysis.

OBJECTIVE: The aim of the study is to evaluate the scientific interest, the collaboration patterns and the emerging trends regarding HPV+ OPSCC diagnosis and treatment. MATERIALS AND METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

3D-printed boluses for radiotherapy: influence of geometrical and printing parameters on dosimetric characterization and air gap evaluation.

The work investigates the implementation of personalized radiotherapy boluses by means of additive manufacturing technologies. Boluses materials that are currently used need an excessive amount of human intervention which leads to reduced repeatability in terms of dosimetry. Additive manufacturing can solve this problem by eliminating the human factor in the process of fabrication. Planar boluses with fixed geometry and personalized boluses printed starting from a computed tomography scan of a radiotherapy phantom were produced. First, a dosimetric characterization study on planar bolus designs to quantify the effects of print parameters such as infill density and geometry on the radiation beam was made. Secondly, a volumetric quantification of air gap between the bolus and the skin of the patient as well as dosimetric analyses were performed. The optimization process according to the obtained dosimetric and airgap results allowed us to find a combination of parameters to have the 3D-printed bolus performing similarly to that in conventional use. These preliminary results confirm those in the relevant literature, with 3D-printed boluses showing a dosimetric performance similar to conventional boluses with the additional advantage of being perfectly conformed to the patient geometry.

Radiation therapy, tissue radiosensitization, and potential synergism in the era of novel antibody-drug conjugates.

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.

Hippocampal region avoidance in whole brain radiotherapy in brain metastases: For all or for some? A real-world feasibility report.

PURPOSE: Hippocampal sparing whole-brain radiotherapy (HS-WBRT) showed significantly lower long-term side effects compared to standard WBRT. Aim of this study is to describe a HS-WBRT real-world monoinstitutional experience within a retrospective cohort. METHODS: Patients who completed HS-WBRT course, with Karnofsky Performance Status ⩾ 60 and radiological diagnosis of brain metastases (BMs) were enrolled. Treatment was performed using helical Tomotherapy scheduled in 30 Gy in 10 or 12 fractions or 25 Gy in 10 fractions. Oncological outcomes were clinically and radiologically assessed every three months. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.3. RESULTS: One hundred and nineteen patients from 2016 to 2020 met inclusion criteria; after a median follow-up of 18 months, 29 patients were alive; 6- and 12-months overall survival rates were 66% and 41%, respectively. HS-WBRT response was assessed for 72 patients. Median time to any progression and intracranial failure (IF) was 4.5 and 13.7 months, respectively. The 6- and 12-month IF rates were 85% and 57%. Among 40 patients (34%) who experienced IF, 17 (42%) were oligometastatic, 23 (58%) polymetastatic and 15/40 developed IF within the hippocampi avoidance zone. No grade (G) ⩾ 2 acute toxicities were reported and one G2 (dizziness) late toxicity was described. CONCLUSIONS: HS-WBRT is well tolerated, and despite the hippocampal sparing region, the oncological control is satisfying. Further investigation is warranted to find patients who could most benefit from a HS-WBRT approach.

Sterotactic Ablative Radiotherapy in a Multicentric Series of Oligometastatic SCLC: The SAMOS Cohort.

AIMS: SCLC is the most aggressive lung cancer histology with a 5-year OS <10%. At the diagnosis, almost two-thirds of the SCLC an Extended Disease presentation. Two randomized studies (CASPIAN and ImPower133) demonstrated an OS improvement, when immunotherapy was prescribed as maintenance therapy after standard chemotherapy. To date, SABR has had a limited indication in managing metastatic SCLC, although recent reports proposed it as a valid treatment option in selected patients. We propose a retrospective multicentric analysis of patients treated with SABR for oligometastatic SCLC. METHOD: Data of patients affected by oligometastatic-SCLC treated with SABR between 2017 and 2022 in 11 Italian centers were collected. Clinical and therapeutic variables together with OS and time to next treatment were analyzed. Univariate analysis with Kaplan-Meier curve were calculated, and log-rank test were applied. Cox proportional hazard model was used for multivariate analysis. RESULTS: Data from 93 patients and 132 metastatic lesions were analyzed. The median age was 64 years (36-86) and all but 1 had Performance Status 0 or 1. Fifty-two patients presented ED at diagnosis. The first line treatment was radiochemotherapy in 42%, CHT alone in 24% and CHT-IO in 28%, others treatment accounts for 4% and only 2% of patients underwent best supportive care. Of the 132 lesions treated with SBRT 55 were in brain, 27 in lung, 11 in liver, 10 in lymph nodes, 8 in bones and 20 in adrenal gland. Median OS was 14 months, 1 year-OS and 2 years OS were 53% and 27%, respectively. The median TtNT was 14 months for the entire population. Of all the analyzed variables only, the anatomical site of the metastases and their number showed statistical significance in the univariate analysist, confirmed in the subsequent multivariate. CONCLUSION: SABR seems to play a role in delaying further systemic lines in oligometastatic disease and to extend the use of ongoing treatment in oligoprogressive state. Prospective studies are needed to confirm these findings.

Intra- and inter-fraction breath-hold variations and margins for radiotherapy of abdominal targets.

Radiotherapy in expiration breath-hold (EBH) has the potential to reduce treatment volumes of abdominal targets compared to an internal target volume concept in free-breathing. The reproducibility of EBH and required safety margins were investigated to quantify this volumetric benefit. Pre- and post-treatment diaphragm position difference and the positioning variability were determined on computed tomography. Systematic and random errors for EBH position reproducibility and positioning variability were calculated, resulting in margins of 7 to 12 mm depending on the prescription isodose and fractionation. A reduced volume was shown for EBH for lesions with superior-inferior breathing motion above 4 to 8 mm.

More than Five Decades of Proton Therapy: A Bibliometric Overview of the Scientific Literature.

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.

Oral Surgery and Osteoradionecrosis in Patients Undergoing Head and Neck Radiation Therapy: An Update of the Current Literature.

Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from avascular aseptic necrosis due to irradiated bone damage. ORN is challenging to treat and can lead to severe complications. Furthermore, ORN causes pain and distress, significantly reducing the patient's quality of life. There is currently no established preventive strategy. This narrative review aims to provide an update for the clinicians on the risk of ORN associated with oral surgery in head and neck RT patients, with a focus on the timing suitable for the oral surgery and possible ORN preventive treatments. An electronic search of articles was performed by consulting the PubMed database. Intervention and observational studies were included. A multidisciplinary approach to the patient is highly recommended to mitigate the risk of RT complications. A dental visit before commencing RT is highly advised to minimize the need for future dental extractions after irradiation, and thus the risk of ORN. Post-RT preventive strategies, in case of dento-alveolar surgery, have been proposed and include antibiotics, hyperbaric oxygen (HBO), and the combined use of pentoxifylline and tocopherol ("PENTO protocol"), but currently there is a lack of established standards of care. Some limitations in the use of HBO involve the low availability of HBO facilities, its high costs, and specific clinical contraindications; the PENTO protocol, on the other hand, although promising, lacks clinical trials to support its efficacy. Due to the enduring risk of ORN, removable prostheses are preferable to dental implants in these patients, as there is no consensus on the appropriate timing for their safe placement. Overall, established standards of care and high-quality evidence are lacking concerning both preventive strategies for ORN as well as the timing of the dental surgery. There is an urgent need to improve research for more efficacious clinical decision making.

Investigating Nutritional and Inflammatory Status as Predictive Biomarkers in Oligoreccurent Prostate Cancer-A RADIOSA Trial Preliminary Analysis.

(1) Background: In the RADIOSA phase II randomized clinical trial (NCT03940235), the biology task entails the identification of predictive and prognostic biomarkers in the context of oligorecurrent, castration-sensitive prostate cancer in order to distinguish polymetastatic from oligometastatic disease. This may lay the groundwork for personalized treatments for those patients who could really benefit from metastasis-directed therapies. (2) Methods: Oligorecurrent PCa pts with three or fewer bone or lymph nodal localizations were randomized 1:1 to receive SBRT alone (arm A) or SBRT + 6 months of ADT (arm B). Common serum-derived biomarkers were collected at baseline, and at 3 months after RT. The prognostic nutritional index, an immune and nutrition-based prognostic score, and the controlling nutritional status (CONUT) score, a scoring system for evaluating patient's nutritional status, were calculated in accordance with the body of available literature. As inflammatory indicators, neutrophil-lymphocyte ratio (NLR) and the NLR-albumin ratio (NLRAR) were assessed. Changes in these parameters between baseline and the 3-month timepoint were evaluated both in absolute and relative values. Changes in these parameters between baseline and the 3-month timepoint were evaluated. Significant differences in the trend of these parameters were assessed using the non-parametric Wilcoxon rank-sum test. A network analysis to analyze the relationships between different features stratifying patients according to the arm of study and site of metastases was performed. (3) Results: The current analysis comprised 88 patients (45 arm A, SBRT only, and 43 arm B, SBRT + ADT). When patients were stratified by ADT administration, cholesterol values showed an increasing trend in the group receiving ADT (p = 0.005) which was no longer significant at 1 year. When patients were stratified by site of metastases (52 lymph nodal, 29 bone localizations), the value of NLR was found to be increased in patients with bone localizations (p < 0.05). In addition, the network analysis showed that BMI and NRI are strongly and directly linked for patients at baseline and that this correlation is no longer found at three months. Finally, when patients were divided according to time from surgery to oligorecurrence (enrollment) the patients with a longer time (>6.7 years) showed an increase in CONUT score from baseline. All the other nutritional and inflammatory scores or parameters investigated in the present analysis showed no statistically significant differences at baseline, three months, 1 year, and in absolute change. (4) Conclusions: The nutritional and inflammatory parameters do not seem to represent valuable candidates for possible use in clinical decision making in our cohort of patients and a reliable biological characterization of the oligometastatic state in prostate cancer still seems far from being achieved. Ongoing molecular analysis will show if there is a role of mutational landscape in the definition of the oligometastatic state.

Cyberknife Radiosurgery for Prostate Cancer after Abdominoperineal Resection (CYRANO): The Combined Computer Tomography and Electromagnetic Navigation Guided Transperineal Fiducial Markers Implantation Technique.

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.

Automatic Segmentation with Deep Learning in Radiotherapy.

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.

A Bibliometric Analysis of the Oligometastatic State over the Last Two Decades: A Shifting Paradigm for Oncology? An AIRO Oligometastatic Study Group.

The term "oligometastasis" represents a relatively novel idea, which denotes a condition characterized by cancer dissemination with a limited number of lesions (usually fewer than five). The aim of the present study is to report a bibliometric analysis of the oligometastatic disease/state, incorporating all relevant studies on the topic for more than 20 years. The research strategy included at least one the terms "Oligmetastases", "Oligometastasis", "Oligometastatic", "Oligoprogression, "Oligoprogressive", "Oligorecurrent", or "Oligorecurrency" in the title, abstract, and/or keywords. All English-language documents from 1 January 1995 (the year of the earliest available document in Scopus) to 31 December 2022 were considered for the analysis. R code (R version 4.2.0) with R Studio (version 2022.12.0-353) and the Bibliometrix package (version 4.0.1) were used for the analysis. A total of 3304 documents, mainly articles (n = 2083, 63.0%) and reviews (n = 813, 24.6%), were collected from 1995 to 2022. The average annual growth rate of literature on the topic was 26.7%. Overall 15,176 authors published on the topic, with an average of eight authors/publication. From 1995, 69 countries contributed to the literature, with the USA and Italy being the top contributors. Among all keywords used by authors, the top three were oligometastases (19%), SBRT (18%), and radiation therapy (8%). Themes regarding "locoregional treatment", "organ motion", and "immunotherapy" were the most recent trend topics, mainly developed from 2019 to 2022, while "high-dose chemotherapy", "whole-brain radiotherapy", and "metastatic breast cancer" saw their main development during 2009-2018. Our study shows the exceptionally flourishing scientific production on the oligometastatic state, summarizing the most influential studies and highlighting the future developments and interests. This analysis will serve as a benchmark to identify this area for the attention of researchers worldwide and contribute to the increasing scientific work.

What is the best time for postoperative radiation therapy in pN1 prostate cancer?

We retrospectively compared long-term biochemical recurrence rates (BCR) in pN1 PCa patients that underwent adjuvant radiotherapy (aRT) vs. no aRT/early salvage (esRT) after robot-assisted radical prostatectomy and extended pelvic lymphadenectomy. All PCa pN1 M0 patients treated at a single high-volume center between 2010 and 2020 were analyzed. Patients with <10 LNs yield, or >10 positive LNs, or persistently detectable PSA after RARP were excluded. Kaplan-Meier (KM) plots depicted BCR rates. Multivariable Cox regression models (MCRMs) focused on predictors of BCR. The cumulative incidence plot depicted BCR rates after propensity score (PS) matching (ratio 1:1). 220 pN1 patients were enrolled, 133 (60.4%) treated with aRT and 87 (39.6%) with no-aRT/esRT. aRT patients were older, with higher rates of postoperative ISUP grade group 4-5, and higher rates of pT3b stage. The actuarial BCR was similar (aRT 39.8% vs. no-aRT/esRT 40.2%; p=1). Median time to BCR was 62 vs. 38 months in aRT vs. no-aRT/esRT patients (p=0.001). In MCRMs, patients managed with no-aRT/esRT were associated with higher rates of BCR over time (hazard ratio [HR]: 3.27, p<0.001). ISUP grade group 5 (HR: 2.18, p<0.01) was an independent predictor of BCR. In PS-matched cumulative incidence plots, the BCR rate was significantly higher in the aRT group (76.4 vs. 40.4%; p<0.01). Patients managed with no-aRT/esRT experienced BCR approximately two years before the aRT group. Despite, the important BCR benefit after aRT, this treatment strategy is underused in daily practice.

Proton Beam Therapy in the Oligometastatic/Oligorecurrent Setting: Is There a Role? A Literature Review.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS) with conventional photon radiotherapy (XRT) are well-established treatment options for selected patients with oligometastatic/oligorecurrent disease. The use of PBT for SABR-SRS is attractive given the property of a lack of exit dose. The aim of this review is to evaluate the role and current utilisation of PBT in the oligometastatic/oligorecurrent setting. METHODS: Using Medline and Embase, a comprehensive literature review was conducted following the PICO (Patients, Intervention, Comparison, and Outcomes) criteria, which returned 83 records. After screening, 16 records were deemed to be relevant and included in the review. RESULTS: Six of the sixteen records analysed originated in Japan, six in the USA, and four in Europe. The focus was oligometastatic disease in 12, oligorecurrence in 3, and both in 1. Most of the studies analysed (12/16) were retrospective cohorts or case reports, two were phase II clinical trials, one was a literature review, and one study discussed the pros and cons of PBT in these settings. The studies presented in this review included a total of 925 patients. The metastatic sites analysed in these articles were the liver (4/16), lungs (3/16), thoracic lymph nodes (2/16), bone (2/16), brain (1/16), pelvis (1/16), and various sites in 2/16. CONCLUSIONS: PBT could represent an option for the treatment of oligometastatic/oligorecurrent disease in patients with a low metastatic burden. Nevertheless, due to its limited availability, PBT has traditionally been funded for selected tumour indications that are defined as curable. The availability of new systemic therapies has widened this definition. This, together with the exponential growth of PBT capacity worldwide, will potentially redefine its commissioning to include selected patients with oligometastatic/oligorecurrent disease. To date, PBT has been used with encouraging results for the treatment of liver metastases. However, PBT could be an option in those cases in which the reduced radiation exposure to normal tissues leads to a clinically significant reduction in treatment-related toxicities.

Conditional survival of patients with low-risk prostate cancer: Temporal changes in active surveillance permanence over time.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.