Genetic profiling in radiotherapy: a comprehensive review.

This comprehensive review explores the pivotal role of radiotherapy in cancer treatment, emphasizing the diverse applications of genetic profiling. The review highlights genetic markers for predicting radiation toxicity, enabling personalized treatment planning. It delves into the impact of genetic profiling on radiotherapy strategies across various cancer types, discussing research findings related to treatment response, prognosis, and therapeutic resistance. The integration of genetic profiling is shown to transform cancer treatment paradigms, offering insights into personalized radiotherapy regimens and guiding decisions in cases where standard protocols may fall short. Ultimately, the review underscores the potential of genetic profiling to enhance patient outcomes and advance precision medicine in oncology.

Identification of perineural invasion at imaging staging as a novel potential risk factor in rectal cancer: A case report.

Treatment of rectal cancer has improved over the years thanks to a multidisciplinary approach. A correct staging has a fundamental role for risk stratification and to define the best treatment for each patient. Unfortunately, approximately 30% of patients with locally advanced rectal cancers will experience tumor recurrence. Thus, the identification of novel clinical-pathological and radiological prognostic factors represents an urgent unmet clinical need. Here we report the case of a patient with radically resected localized rectal cancer who developed an impressive early pelvic recurrence. To better understand the clinical scenario, we have studied the possible factors related to the aggressiveness of the disease. The only poor prognosticfactor that was evidenced at histological report was perineural invasion. Therefore, we questioned whether we could evaluate perineural invasion with imaging, similar to head and neck tumors. Learning from this clinical case, we believe that improving the risk stratification and radiology reporting is necessary to provide the best care for the patient and allow for a better prognosis prediction. Of course, our data should be considered as hypothesis generating and should be further investigated and validated in larger and prospective studies.

Preliminary Experience in Ultra-High Frequency Ultrasound Assessment of Cutaneous Primary Lymphomas: An Innovative Classification.

BACKGROUND: Primary cutaneous lymphoma (PCL) is a rare form of extranodal non-Hodgkin's lymphoma characterized by malignant lymphocytes confined to the skin. Accurate diagnosis and staging are crucial for optimal management, yet radiological literature on imaging PCL remains limited. This study aims to delineate the imaging characteristics of PCLs using high and ultra-high frequency ultrasound (UHFUS) and proposes a classification system based on ultrasound findings. METHODS: A cohort of 88 individuals with suspected PCL underwent high-resolution ultrasound (HRUS) and color Doppler examination of lesions. Lesions were categorized based on sonographic appearance, and subsequent histopathological assessment confirmed the diagnosis. RESULTS: Ultrasound imaging revealed distinct patterns for primary cutaneous T-cell lymphomas (PCTCL) and primary cutaneous B-cell lymphomas (PCBCL), with characteristic features such as hypoechoic nodules, pseudonodular lesions, and dermal infiltration. Histopathological analysis confirmed the ultrasound findings, supporting the proposed classification system. CONCLUSIONS: Ultrasonography, particularly UHFUS, offers valuable insights into the imaging characteristics of primary cutaneous lymphomas, aiding the accurate diagnosis and assessment of treatment response. The proposed classification system based on ultrasound findings enhances the diagnostic approach to PCLs, and paves the way for improved patient care and management strategies.

Delta radiomics: an updated systematic review.

BACKGROUND: Radiomics can provide quantitative features from medical imaging that can be correlated with various biological features and diverse clinical endpoints. Delta radiomics, on the other hand, consists in the analysis of feature variation at different acquisition time points, usually before and after therapy. The aim of this study was to provide a systematic review of the different delta radiomics approaches. METHODS: Eligible articles were searched in Embase, Pubmed, and ScienceDirect using a search string that included free text and/or Medical Subject Headings (MeSH) with 3 key search terms: 'radiomics,' 'texture,' and 'delta.' Studies were analyzed using QUADAS-2 and the RQS tool. RESULTS: Forty-eight studies were finally included. The studies were divided into preclinical/methodological (5 studies, 10.4%); rectal cancer (6 studies, 12.5%); lung cancer (12 studies, 25%); sarcoma (5 studies, 10.4%); prostate cancer (3 studies, 6.3%), head and neck cancer (6 studies, 12.5%); gastrointestinal malignancies excluding rectum (7 studies, 14.6%) and other disease sites (4 studies, 8.3%). The median RQS of all studies was 25% (mean 21% ± 12%), with 13 studies (30.2%) achieving a quality score < 10% and 22 studies (51.2%) < 25%. CONCLUSIONS: Delta radiomics shows potential benefit for several clinical endpoints in oncology, such asdifferential diagnosis, prognosis and prediction of treatment response, evaluation of side effects. Nevertheless, the studies included in this systematic review suffer from the bias of overall low methodological rigor, so that the conclusions are currently heterogeneous, not robust and hardly replicable. Further research with prospective and multicenter studies is needed for the clinical validation of delta radiomics approaches.

Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: A retrospective analysis.

BACKGROUND: Cemiplimab, a programmed cell death-1 inhibitor approved in 2018 for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) who are ineligible for curative therapies, lacks clarity regarding the optimal patient selection despite its known efficacy. OBJECTIVE: This retrospective study aims to assess the real-world treatment patterns and outcomes in patients with cSCC at our institution. METHODS: A retrospective analysis of consecutively treated patients with cemiplimab for cSCC was conducted. Progression-free survival (PFS) and overall survival were evaluated alongside clinical-pathologic characteristics. RESULTS: Forty-five patients were included, of which 73.3% were male with a median age of 77 years. After 18 months of median follow-up median PFS and overall survival were not reached with a mean of 21.3 months ± 2.2 months and 25.3 ± 2.1 months, respectively. Univariate and multivariate analyses revealed significant correlations only between PFS and previous radiotherapy (P values: .043 and .046, respectively). LIMITATIONS: Limitations include its retrospective nature, the low number of patients analyzed, and the potential for inherent biases. CONCLUSIONS: The study reveals a significant association between prior radiotherapy and improved PFS in cemiplimab-treated cSCC, suggesting the potential for combining radiotherapy with cemiplimab. Further exploration of this combined approach is warranted.

Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial.

BACKGROUND: CAVE is a single arm, Phase 2 trial, that demonstrated anti-tumor activity of cetuximab rechallenge plus avelumab in patients with RAS wild type (wt) metastatic colorectal cancer (mCRC). OBJECTIVE: We conducted a post hoc analysis to identify potential radiomic biomarkers for patients with CRC liver metastasis (LM). PATIENTS AND METHODS: Patients with LM that could be measured by enhanced contrast phase computed tomography (CT) imaging at baseline and at first response evaluation were included. Multiple texture parameters were extracted with the LifeX Software. Delta-texture (D-TA) variations were calculated by comparing data at baseline and after treatment. RESULTS: Overall, 55/77 patients (71%) had LM; 39 met the inclusion criteria for the current analysis. The D-TA parameters that significantly correlated at univariate analysis with median progression-free survival (mPFS) were EntropyHistogram (p = 0.021), HomogeneityGLCM (p < 0.001) and Dissimilarity GLCM (p = 0.002). At multivariate analysis, only HomogeneityGLCM resulted significant for PFS (p = 0.001). Patients (19/39, 48.7%) with reduction of HomogeneityGLCM experienced better mPFS (4.6 vs 2.9 months; HR 0.45; 95% CI 0.23-0.88; p = 0.021) and median overall survival (mOS) (17.3 vs 6.8 months; HR 0.40, 95% CI 0.21-0.80; p = 0.010). A trend to better mPFS, was also observed in patients with RAS/BRAF wt circulating tumor DNA and reduction of HomogeneityGLCM. Overall survival was significantly better in this subgroup of patients with low HomogeneityGLCM: mOS was 17.8 (95% CI 15.5-20.2) versus 6.8 months (95% CI 3.6-10.0) (HR 0.34, 95% CI 0.14-0.81; p = 0.016). CONCLUSION: Reduction in the D-TA parameter HomogeneityGLCM by radiomic analysis correlates with improved outcomes in patients with LM receiving cetuximab rechallenge plus avelumab therapy. Larger prospective studies are needed to validate and confirm these findings.

All for one: Collaboration between dermatologist, radiation oncologist and radiologist in the clinical management of "difficult to treat" non melanoma skin cancer.

This series introduces the clinical management of difficult-to-treat non-melanoma skin cancers (NMSCs) through a multidisciplinary approach, emphasizing the integration of dermoscopy and Ultra high-frequency ultrasound (UHFUS) for accurate diagnosis and treatment planning, particularly in cases referred for radiotherapy (RT). Dermoscopy aids in diagnosing both pigmented and non-pigmented skin lesions, guiding treatment margins and reducing the benign-to-malignant biopsy ratio. UHFUS provides valuable insights into tumor size, depth, and vascularity, complementing clinical evaluations and assisting in RT planning. Three challenging cases are presented, highlighting the pivotal role of dermoscopy and UHFUS in decision-making and treatment optimization. Collaboration between dermatologists, radiation oncologists, and radiologists enhances diagnostic accuracy, tailoring treatment plans to individual patient needs and preferences, ultimately improving patient outcomes and experience. The integration of these imaging techniques holds promise for optimizing non-surgical treatments like RT and monitoring treatment progress, offering a personalized approach to NMSC management.

Artificial Intelligence-suggested Predictive Model of Survival in Patients Treated With Stereotactic Radiotherapy for Early Lung Cancer.

BACKGROUND/AIM: Overall survival (OS)-predictive models to clinically stratify patients with stage I Non-Small Cell Lung Cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) are still unavailable. The aim of this work was to build a predictive model of OS in this setting. PATIENTS AND METHODS: Clinical variables of patients treated in three Institutions with SBRT for stage I NSCLC were retrospectively collected into a reference cohort A (107 patients) and 2 comparative cohorts B1 (32 patients) and B2 (38 patients). A predictive model was built using Cox regression (CR) and artificial neural networks (ANN) on reference cohort A and then tested on comparative cohorts. RESULTS: Cohort B1 patients were older and with worse chronic obstructive pulmonary disease (COPD) than cohort A. Cohort B2 patients were heavier smokers but had lower Charlson Comorbidity Index (CCI). At CR analysis for cohort A, only ECOG Performance Status 0-1 and absence of previous neoplasms correlated with better OS. The model was enhanced combining ANN and CR findings. The reference cohort was divided into prognostic Group 1 (0-2 score) and Group 2 (3-9 score) to assess model's predictions on OS: grouping was close to statistical significance (p=0.081). One and 2-year OS resulted higher for Group 1, lower for Group 2. In comparative cohorts, the model successfully predicted two groups of patients with divergent OS trends: higher for Group 1 and lower for Group 2. CONCLUSION: The produced model is a relevant tool to clinically stratify SBRT candidates into prognostic groups, even when applied to different cohorts. ANN are a valuable resource, providing useful data to build a prognostic model that deserves to be validated prospectively.

Advances in traditional Chinese herbal medicine and their pharmacodynamic mechanisms in cancer immunoregulation: a narrative review.

Background and Objective: The cancer-immunity cycle (CIC) is defined as a series of progressive events that cause an anticancer immune response leading to the killing of the cancer cell. The concept of CIC has important guiding significance for the clinical and basic tumor immunotherapy research. As one of the methods of traditional Chinese medicine (TCM), Chinese herbal medicine (CHM) has shown unique advantages in multitarget and multipathway immune regulation. However, the tumor immune circulation targeted by CHM is generally unclear at present. To provide reference for future clinical and basic research, we systematically reviewed the existing literature on CHM (including CHM monomers, CHM compounds, and CHM patent medicines) and the mechanisms related to its efficacy. Methods: We searched the PubMed and China National Knowledge Infrastructure (CNKI) databases for relevant Chinese-language and English-language literature published from January 1988 to October 2022. The literature was screened manually at three levels: title, abstract, and full text, to identify articles related to CHM and their mechanism of regulating tumor immunity. Key Content and Findings: By further classifying the CIC, it was confirmed that CHM can regulate the activation of dendritic cells (DCs) and macrophages and promote the presentation of tumor antigens. Meanwhile, CHM can also reverse tumor-immune escape by enhancing T-cell proliferation and infiltration. In addition, CHM can also enhance the antitumor ability of the body by regulating the killing process of tumor cells. Conclusions: The theory of a CIC is of guiding significance to regulating tumor immunity via CHM.

Redetermination of PD-L1 expression after chemio-radiation in locally advanced PDL1 negative NSCLC patients: retrospective multicentric analysis.

Background: Chemoradiation therapy (CRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CRT on tumor cells programmed cell death ligand-1 (PD-L1) expression is unknown. Methods: In this multicentric retrospective study, we analyzed paired NSCLC specimens that had been obtained pre- and post-CRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. The purpose of this study was to evaluate the feasibility, risk of complications, and clinical relevance of performing re-biopsy after CRT in patients with PD-L1 negative LA-NSCLC. Results: Overall, 31 patients from 6 centers with PD-L1 negative LA-NSCLC were analyzed. The percentage of tumor cells with PD-L1 expression significantly increased between pre- and post-CRT specimens in 14 patients (45%). Nine patients had unchanged PD-L1 expression after CRT, in five patients the rebiopsy material was insufficient for PD-L1 analysis and in two patients no tumor cells at rebiopsy were found. The post-rebiopsy complication rate was very low (6%). All patients with positive PD-L1 re-biopsy received Durvalumab maintenance after CRT, except one patient who had a long hospitalization for tuberculosis reactivation. Median PFS of patients with unchanged or increased PD-L1 expression was 10 and 16.9 months, respectively. Conclusion: CRT administration can induce PD-L1 expression in a considerable fraction of PD-L1 negative patients at baseline, allowing them receiving the maintenance Durvalumab in Europe. Hence, after a definitive CRT, PD-L1 redetermination should be considered in patients with LA-NSCLC PD-L1 negative, to have a better selection of maintenance Durvalumab candidates.

Artificial intelligence applied to image-guided radiation therapy (IGRT): a systematic review by the Young Group of the Italian Association of Radiotherapy and Clinical Oncology (yAIRO).

INTRODUCTION: The advent of image-guided radiation therapy (IGRT) has recently changed the workflow of radiation treatments by ensuring highly collimated treatments. Artificial intelligence (AI) and radiomics are tools that have shown promising results for diagnosis, treatment optimization and outcome prediction. This review aims to assess the impact of AI and radiomics on modern IGRT modalities in RT. METHODS: A PubMed/MEDLINE and Embase systematic review was conducted to investigate the impact of radiomics and AI to modern IGRT modalities. The search strategy was "Radiomics" AND "Cone Beam Computed Tomography"; "Radiomics" AND "Magnetic Resonance guided Radiotherapy"; "Radiomics" AND "on board Magnetic Resonance Radiotherapy"; "Artificial Intelligence" AND "Cone Beam Computed Tomography"; "Artificial Intelligence" AND "Magnetic Resonance guided Radiotherapy"; "Artificial Intelligence" AND "on board Magnetic Resonance Radiotherapy" and only original articles up to 01.11.2022 were considered. RESULTS: A total of 402 studies were obtained using the previously mentioned search strategy on PubMed and Embase. The analysis was performed on a total of 84 papers obtained following the complete selection process. Radiomics application to IGRT was analyzed in 23 papers, while a total 61 papers were focused on the impact of AI on IGRT techniques. DISCUSSION: AI and radiomics seem to significantly impact IGRT in all the phases of RT workflow, even if the evidence in the literature is based on retrospective data. Further studies are needed to confirm these tools' potential and provide a stronger correlation with clinical outcomes and gold-standard treatment strategies.

Magnetic Resonance Imaging Evaluation of Bone Metastases Treated with Radiotherapy in Palliative Intent: A Multicenter Prospective Study on Clinical and Instrumental Evaluation Assessment Concordance (MARTE Study).

Metastasis to bone is a common occurrence among epithelial tumors, with a high incidence rate in the Western world. As a result, bone lesions are a significant burden on the healthcare system, with a high morbidity index. These injuries are often symptomatic and can lead to functional limitations, which in turn cause reduced mobility in patients. Additionally, they can lead to secondary complications such as pathological fractures, spinal cord compression, hypercalcemia, or bone marrow suppression. The treatment of bone metastases requires collaboration between multiple healthcare professionals, including oncologists, orthopedists, neurosurgeons, physiatrists, and radiotherapists. The primary objective of this study is to evaluate the correlation between two methods used to assess local control. Specifically, the study aims to determine if a reduction in the volume of bone lesions corresponds to better symptomatic control in the clinical management of patients, and vice versa. To achieve this objective, the study evaluates morphological criteria by comparing pre- and post-radiotherapy treatment imaging using MRI and RECIST 1.1 criteria. MRI without contrast is the preferred diagnostic imaging method, due to its excellent tolerance by patients, the absence of exposure to ionizing radiation, and the avoidance of paramagnetic contrast media side effects. This imaging modality allows for accurate assessment of bone lesions. One of the secondary objectives of this study is to identify potentially useful parameters that can distinguish patients into two classes: "good" and "poor" responders to treatment, as reported by previous studies in the literature. These parameters can be evaluated from the imaging examinations by analyzing morphological changes and radiomic features on different sequences, such as T1, STIR (short tau inversion recovery), and DWI-MRI (diffusion-weighted).

Chemoradiotherapy for Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is a highly challenging cancer [...].

Artificial intelligence and radiation effects on brain tissue in glioblastoma patient: preliminary data using a quantitative tool.

PURPOSE: The quantification of radiotherapy (RT)-induced functional and morphological brain alterations is fundamental to guide therapeutic decisions in patients with brain tumors. The magnetic resonance imaging (MRI) allows to define structural RT-brain changes, but it is unable to evaluate early injuries and to objectively quantify the volume tissue loss. Artificial intelligence (AI) tools extract accurate measurements that permit an objective brain different region quantification. In this study, we assessed the consistency between an AI software (Quibim Precision® 2.9) and qualitative neruroradiologist evaluation, and its ability to quantify the brain tissue changes during RT treatment in patients with glioblastoma multiforme (GBM). METHODS: GBM patients treated with RT and subjected to MRI assessment were enrolled. Each patient, pre- and post-RT, undergoes to a qualitative evaluation with global cerebral atrophy (GCA) and medial temporal lobe atrophy (MTA) and a quantitative assessment with Quibim Brain screening and hippocampal atrophy and asymmetry modules on 19 extracted brain structures features. RESULTS: A statistically significant strong negative association between the percentage value of the left temporal lobe and the GCA score and the left temporal lobe and the MTA score was found, while a moderate negative association between the percentage value of the right hippocampus and the GCA score and the right hippocampus and the MTA score was assessed. A statistically significant strong positive association between the CSF percentage value and the GCA score and a moderate positive association between the CSF percentage value and the MTA score was found. Finally, quantitative feature values showed that the percentage value of the cerebro-spinal fluid (CSF) statistically differences between pre- and post-RT. CONCLUSIONS: AI tools can support a correct evaluation of RT-induced brain injuries, allowing an objective and earlier assessment of the brain tissue modifications.

CARdioimaging in Lung Cancer PatiEnts Undergoing Radical RadioTherapy: CARE-RT Trial.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a common, steady growing lung tumour that is often discovered when a surgical approach is forbidden. For locally advanced inoperable NSCLC, the clinical approach consists of a combination of chemotherapy and radiotherapy, eventually followed by adjuvant immunotherapy, a treatment that is useful but may cause several mild and severe adverse effect. Chest radiotherapy, specifically, may affect the heart and coronary artery, impairing heart function and causing pathologic changes in myocardial tissues. The aim of this study is to evaluate the damage coming from these therapies with the aid of cardiac imaging. METHODS: This is a single-centre, prospective clinical trial. Patients with NSCLC who are enrolled will undergo computed tomography (CT) and magnetic resonance imaging (MRI) before chemotherapy 3 months, 6 months, and 9-12 months after the treatment. We expect to enrol 30 patients in 2 years. CONCLUSIONS: Our clinical trial will be an opportunity not only to highlight the timing and the radiation dose needed for pathological cardiac tissue changes to happen but will also provide useful data to set new follow-up schedules and strategies, keeping in mind that, more often than not, patients affected by NSCLC may present other heart- and lung-related pathological conditions.

Role of Cardiac Biomarkers in Non-Small Cell Lung Cancer Patients.

Treatment-induced cardiac toxicity represents an important issue in non-small cell lung cancer (NSCLC) patients, and no biomarkers are currently available in clinical practice. A novel and easy-to-calculate marker is the quantitative analysis of calcium plaque in the coronary, calculated on CT. It is called the Agatston score (or CAD score). At the same time, other potential predictors include cardiac ultrasonography and anamnesis of the patients. Our work aimed to correlate cardiac biomarkers with overall survival (OS) in NSCLC patients. We retrospectively analyzed patients with NSCLC discussed in the Multidisciplinary Tumor Board of our Institute for the present analysis between January 2018 and July 2022. Inclusion criteria were the availability of basal CT imaging of the thorax, cardiac ultrasonography with the calculation of ejection fraction (EF), and complete anamnesis, including assessment of co-pathologies and pharmacological drugs. The clinical data of the patients were retrospectively collected, and the CAD scores was calculated on a CT scan. All of these parameters were correlated with overall survival (OS) with univariate analysis (Kaplan-Meier analysis) and multivariate analysis (Cox regression analysis). Following the above-mentioned inclusion criteria, 173 patients were included in the present analysis. Of those, 120 patients died in the follow-up period (69.6%), and the median overall survival (OS) was 28 months (mean 47.2 months, 95% CI, 36-57 months). In univariate analysis, several parameters that significantly correlated with lower OS were the stage (p < 0.001), the CAD grading (p < 0.001), history of ischemic heart disease (p: 0.034), use of beta blocker drugs (p: 0.036), and cardiac ejection fraction (p: 0.005). In multivariate analysis, the only parameters that remained significant were as follows: CAD score (p: 0.014, OR 1.56, 95% CI: 1.04-1.83), stage (p: 0.016, OR: 1.26, 95% CI: 1.05-1.53), and cardiac ejection fraction (p: 0.011, OR 0.46, 95% CI: 0.25-0.84). Both CAD score and ejection fraction are correlated with survival in NSCLC patients at all stages of the disease. Independently from the treatment choice, a cardiological evaluation is mandatory for patients with NSCLC.