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.
Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER ...registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation.
All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks.
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.
(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.
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.
The literature on PT until the 31st December 2022 in the Scopus database was searched, including the following keywords:
AND
AND
/
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.
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,
, and
deserve to be highlighted.
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.
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 (
= 2083, 63.0%) and reviews (
= 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.
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).
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.
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 (
= 0.020) and PFS (
= 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.
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.
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.
Currently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for ...both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics.
MONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building.
Thanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients.
The study was prospectively registered at clinicaltrials.gov (NCT05974475).
The current study aims to profile sarcopenic condition (both at baseline and developed during treatment) in oropharyngeal carcinoma (OPC) patients treated with curative radiotherapy (RT) +/- ...chemotherapy and to evaluate its impact on oncological outcomes and toxicity. A total of 116 patients were included in this retrospective single-center study. Sarcopenia assessment at baseline and at 50 Gy re-evaluation CT was obtained from two different methodologies: (i) the L3-skeletal muscle index (SMI) derived from the contouring of the cross-sectional area (CSA) of the masticatory muscles (CSA-MM); and (ii) the paravertebral and sternocleidomastoid muscles at the level of the third cervical vertebra (CSA-C3). Based on L3-SMI from CSA-MM, developing sarcopenic condition during RT (on-RT sarcopenia) was associated with worse progression-free survival (PFS) (
= 0.03) on multivariable analysis and a trend of correlation with overall survival (OS) was also evident (
= 0.05). According to L3-SMI derived from CSA-C3, on-RT sarcopenia was associated with worse PFS (
= 0.0096) and OS (
= 0.013) on univariate analysis; these associations were not confirmed on multivariable analysis. A significant association was reported between becoming on-RT sarcopenia and low baseline haemoglobin (
= 0.03) and the activation of nutritional counselling (
= 0.02). No significant associations were found between sarcopenia and worse RT toxicity. Our data suggest that the implementation of prompt nutritional support to prevent the onset of sarcopenia during RT could improve oncological outcomes in OPC setting.
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.
