Impact of image filtering and assessment of volume-confounding effects on CT radiomic features and derived survival models in non-small cell lung cancer

BACKGROUND No evidence supports the choice of specific imaging filtering methodologies in radiomics. As the volume of the primary tumor is a well-recognized prognosticator, our purpose is to assess how filtering may impact the feature/volume dependency in computed tomography (CT) images of non-small cell lung cancer (NSCLC), and if such impact translates into differences in the performance of survival modeling. The role of lesion volume in model performances was also considered and discussed. METHODS Four-hundred seventeen CT images NSCLC patients were retrieved from the NSCLC-Radiomics public repository. Pre-processing and features extraction were implemented using Pyradiomics v3.0.1. Features showing high correlation with volume across original and filtered images were excluded. Cox proportional hazards (PH) with least absolute shrinkage and selection operator (LASSO) regularization and CatBoost models were built with and without volume, and their concordance (C-) indices were compared using Wilcoxon signed-ranked test. The Mann Whitney U test was used to assess model performances after stratification into two groups based on low- and high-volume lesions. RESULTS Radiomic models significantly outperformed models built on only clinical variables and volume. However, the exclusion/inclusion of volume did not generally alter the performances of radiomic models. Overall, performances were not substantially affected by the choice of either imaging filter (overall C-index 0.539-0.590 for Cox PH and 0.589-0.612 for CatBoost). The separation of patients with high-volume lesions resulted in significantly better performances in 2/10 and 7/10 cases for Cox PH and CatBoost models, respectively. Both low- and high-volume models performed significantly better with the inclusion of radiomic features (P<0.0001), but the improvement was largest in the high-volume group (+10.2% against +8.7% improvement for CatBoost models and +10.0% against +5.4% in Cox PH models). CONCLUSIONS Radiomic features complement well-known prognostic factors such as volume, but their volume-dependency is high and should be managed with vigilance. The informative content of radiomic features may be diminished in small lesion volumes, which could limit the applicability of radiomics in early-stage NSCLC, where tumors tend to be small. Our results also suggest an advantage of CatBoost models over the Cox PH models

Unraveling Mitochondrial Determinants of Tumor Response to Radiation Therapy

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

Upfront Advanced Radiotherapy and New Drugs for NSCLC Patients with Synchronous Brain Metastases: Is the Juice Worth the Squeeze? A Real-World Analysis from Lombardy, Italy

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 &euro;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

Upfront Advanced Radiotherapy and New Drugs for NSCLC Patients with Synchronous Brain Metastases: Is the Juice Worth the Squeeze? A Real-World Analysis from Lombardy, Italy

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

Virtual and Augmented Reality as a Novel Opportunity to Unleash the Power of Radiotherapy in the Digital Era: A Scoping Review

Although radiation therapy (RT) provides several therapeutic advantages in terms of cancer control and quality of life, it continues to be a poorly understood field by most students and health workers. Theoretical lessons are not sufficient, while practical exercitations are time-consuming, both in terms of man- and machine-hours. Furthermore, RT candidates often have several prejudices that may affect their treatment choices, favoring the more well-known surgical or chemotherapy approaches or resulting in a high level of anxiety during treatment. Moreover, the misperception of low treatment control and its related side effects could worsen the patients’ psychological distress, already brought by a cancer diagnosis. Augmented reality (AR) and virtual reality (VR) could be a valid instrument for promoting the awareness of radiation oncology as a discipline with its own identity and respect in the scientific community. The aim of the present work is to provide a glance at the recent developments in AR/VR to support students’ education, personnel training and patients’ empowerment in this clinical setting. The main findings of our work show that such technologies have already become a reality in many institutions worldwide and it has been shown to be an effective strategy for raising educational standards, improving health workers’ skills and promoting patients’ well-being and compliance. These results seem to promote the further implementation of AR/VR technologies and their development as a driving force of a much-hoped-for revolution in the way patients are treated and radiation oncology is taught

Virtual and Augmented Reality as a Novel Opportunity to Unleash the Power of Radiotherapy in the Digital Era: A Scoping Review

Although radiation therapy (RT) provides several therapeutic advantages in terms of cancer control and quality of life, it continues to be a poorly understood field by most students and health workers. Theoretical lessons are not sufficient, while practical exercitations are time-consuming, both in terms of man- and machine-hours. Furthermore, RT candidates often have several prejudices that may affect their treatment choices, favoring the more well-known surgical or chemotherapy approaches or resulting in a high level of anxiety during treatment. Moreover, the misperception of low treatment control and its related side effects could worsen the patients&rsquo; psychological distress, already brought by a cancer diagnosis. Augmented reality (AR) and virtual reality (VR) could be a valid instrument for promoting the awareness of radiation oncology as a discipline with its own identity and respect in the scientific community. The aim of the present work is to provide a glance at the recent developments in AR/VR to support students&rsquo; education, personnel training and patients&rsquo; empowerment in this clinical setting. The main findings of our work show that such technologies have already become a reality in many institutions worldwide and it has been shown to be an effective strategy for raising educational standards, improving health workers&rsquo; skills and promoting patients&rsquo; well-being and compliance. These results seem to promote the further implementation of AR/VR technologies and their development as a driving force of a much-hoped-for revolution in the way patients are treated and radiation oncology is taught

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

Prognostic Impact of Sarcopenia&rsquo;s Occurrence during Radiotherapy in Oropharyngeal Cancer Patients

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) +/&minus; 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) (p = 0.03) on multivariable analysis and a trend of correlation with overall survival (OS) was also evident (p = 0.05). According to L3-SMI derived from CSA-C3, on-RT sarcopenia was associated with worse PFS (p = 0.0096) and OS (p = 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 (p = 0.03) and the activation of nutritional counselling (p = 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

Prognostic Impact of Sarcopenia’s Occurrence during Radiotherapy in Oropharyngeal Cancer Patients

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) (p = 0.03) on multivariable analysis and a trend of correlation with overall survival (OS) was also evident (p = 0.05). According to L3-SMI derived from CSA-C3, on-RT sarcopenia was associated with worse PFS (p = 0.0096) and OS (p = 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 (p = 0.03) and the activation of nutritional counselling (p = 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

Dosimetric Evaluation of the Inter-Fraction Motion of Organs at Risk in SBRT for Nodal Oligometastatic Prostate Cancer

In this paper, we aim to evaluate the entity of inter-fraction organ motion and deformation in stereotactic body radiotherapy (SBRT) treatments for nodal oligometastatic prostate cancer (PCa). Thirty-three patients with lymph nodes showing oligometastatic PCa treated with SBRT were included. Organs at risk (OARs) were delineated using both simulation computer tomography (s-CT) and daily cone beam CTs (CBCTs) using the Raystation planning system. For each OAR, the union volume (UV) between all the CBCTs and s-CT was computed. An expanded volume (EV) of the s-CT OARs was applied using six different margins (3, 5, 8, 10, 15, and 20 mm). A percentage volume (V%) was computed to assess the intersection between each EV and UV. The OAR deformation and motion were further evaluated using the dice similarity coefficient (DSC) and mean distance to agreement (Mean_DA). The percentage maximum dose variations for all the OARs were estimated. A recalculation with higher dose prescriptions was performed by prescribing 36 Gy/3 fx, as well as 45 Gy/3 fx. The cauda showed the highest matching (DSC = 0.72; Mean_DA = 0.14 cm), and the colon showed the lowest one (DSC = 0.37; Mean_DA = 0.44 cm). The minimum margin, which ensured a V% &gt; 95%, was 3 mm (97.5%) for the cauda and 15 mm (96.6%) for the colon. All the OARs reached the compliance of the constraints in each session. Regarding 36 Gy-plans, the ileum punctual compliance Dmax failed in 58.8% of patients, and it failed in 70.6% of the patients for the ileum, 7.14% for the colon, and 12.5% for the bladder in the case of 45 Gy-plans. This study is an ancillary study of the RADIOSA clinical trial (AIRC IG-22159) and can be used as a benchmark for dose escalation