Role of artificial intelligence applied to ultrasound in gynecology oncology: A systematic review.

The aim of this paper was to explore the role of artificial intelligence (AI) applied to ultrasound imaging in gynecology oncology. Web of Science, PubMed, and Scopus databases were searched. All studies were imported to RAYYAN QCRI software. The overall quality of the included studies was assessed using QUADAS-AI tool. Fifty studies were included, of these 37/50 (74.0%) on ovarian masses or ovarian cancer, 5/50 (10.0%) on endometrial cancer, 5/50 (10.0%) on cervical cancer, and 3/50 (6.0%) on other malignancies. Most studies were at high risk of bias for subject selection (i.e., sample size, source, or scanner model were not specified; data were not derived from open-source datasets; imaging preprocessing was not performed) and index test (AI models was not externally validated) and at low risk of bias for reference standard (i.e., the reference standard correctly classified the target condition) and workflow (i.e., the time between index test and reference standard was reasonable). Most studies presented machine learning models (33/50, 66.0%) for the diagnosis and histopathological correlation of ovarian masses, while others focused on automatic segmentation, reproducibility of radiomics features, improvement of image quality, prediction of therapy resistance, progression-free survival, and genetic mutation. The current evidence supports the role of AI as a complementary clinical and research tool in diagnosis, patient stratification, and prediction of histopathological correlation in gynecological malignancies. For example, the high performance of AI models to discriminate between benign and malignant ovarian masses or to predict their specific histology can improve the diagnostic accuracy of imaging methods.

Coping with modesty during radiotherapy for breast cancer: a multicentric study.

PURPOSE: Breast cancer is the most frequently diagnosed tumour, representing nearly 30% of all new cases in women. Radiotherapy (RT) plays a crucial role in the management of breast cancer. The objective of this study is to assess modesty in patients undergoing RT for breast cancer and take their suggestions and ideas into consideration to enhance the quality of treatment in this regard. METHODS: The study enrolled 555 breast cancer patients undergoing adjuvant RT in three Italian centres. Patients completed a self-test questionnaire assessing their comfort level concerning modesty during therapy and their relationship with strangers and healthcare professionals. The impact of religious views and potential changes in sexuality were also examined. RESULTS: Results showed that modesty was a common concern across the overall cohort of patients, with discomfort in being undressed during RT correlating with discomfort experienced in other daily life situations. Most patients felt more at ease with same sex healthcare workers. Age was also a major factor with younger patients generally feeling more comfortable with healthcare workers of the same age group. Interestingly, the surgical technique used (mastectomy vs. quadrantectomy) did not significantly influence modesty perceptions. Patients provided valuable suggestions to improve privacy and modesty during RT. CONCLUSION: This study demonstrates that modesty is an important issue for women undergoing RT, which can be influenced by personal characteristics and hospital-related factors. A reflection about the need to address modesty concerns and to incorporate dedicated interventions for protecting patients' physical and emotional well-being is warranted. Initiatives to improve communication, involvement, and body image support should also be integrated into the care path of patients to better their overall therapeutic experience. This study paves the way for broader research and interventions in daily cancer care.

The Image Biomarker Standardization Initiative: Standardized Convolutional Filters for Reproducible Radiomics and Enhanced Clinical Insights.

Filters are commonly used to enhance specific structures and patterns in images, such as vessels or peritumoral regions, to enable clinical insights beyond the visible image using radiomics. However, their lack of standardization restricts reproducibility and clinical translation of radiomics decision support tools. In this special report, teams of researchers who developed radiomics software participated in a three-phase study (September 2020 to December 2022) to establish a standardized set of filters. The first two phases focused on finding reference filtered images and reference feature values for commonly used convolutional filters: mean, Laplacian of Gaussian, Laws and Gabor kernels, separable and nonseparable wavelets (including decomposed forms), and Riesz transformations. In the first phase, 15 teams used digital phantoms to establish 33 reference filtered images of 36 filter configurations. In phase 2, 11 teams used a chest CT image to derive reference values for 323 of 396 features computed from filtered images using 22 filter and image processing configurations. Reference filtered images and feature values for Riesz transformations were not established. Reproducibility of standardized convolutional filters was validated on a public data set of multimodal imaging (CT, fluorodeoxyglucose PET, and T1-weighted MRI) in 51 patients with soft-tissue sarcoma. At validation, reproducibility of 486 features computed from filtered images using nine configurations × three imaging modalities was assessed using the lower bounds of 95% CIs of intraclass correlation coefficients. Out of 486 features, 458 were found to be reproducible across nine teams with lower bounds of 95% CIs of intraclass correlation coefficients greater than 0.75. In conclusion, eight filter types were standardized with reference filtered images and reference feature values for verifying and calibrating radiomics software packages. A web-based tool is available for compliance checking.

Radiomics of Intrahepatic Cholangiocarcinoma and Peritumoral Tissue Predicts Postoperative Survival: Development of a CT-Based Clinical-Radiomic Model.

BACKGROUND: For many tumors, radiomics provided a relevant prognostic contribution. This study tested whether the computed tomography (CT)-based textural features of intrahepatic cholangiocarcinoma (ICC) and peritumoral tissue improve the prediction of survival after resection compared with the standard clinical indices. METHODS: All consecutive patients affected by ICC who underwent hepatectomy at six high-volume centers (2009-2019) were considered for the study. The arterial and portal phases of CT performed fewer than 60 days before surgery were analyzed. A manual segmentation of the tumor was performed (Tumor-VOI). A 5-mm volume expansion then was applied to identify the peritumoral tissue (Margin-VOI). RESULTS: The study enrolled 215 patients. After a median follow-up period of 28 months, the overall survival (OS) rate was 57.0%, and the progression-free survival (PFS) rate was 34.9% at 3 years. The clinical predictive model of OS had a C-index of 0.681. The addition of radiomic features led to a progressive improvement of performances (C-index of 0.71, including the portal Tumor-VOI, C-index of 0.752 including the portal Tumor- and Margin-VOI, C-index of 0.764, including all VOIs of the portal and arterial phases). The latter model combined clinical variables (CA19-9 and tumor pattern), tumor indices (density, homogeneity), margin data (kurtosis, compacity, shape), and GLRLM indices. The model had performance equivalent to that of the postoperative clinical model including the pathology data (C-index of 0.765). The same results were observed for PFS. CONCLUSIONS: The radiomics of ICC and peritumoral tissue extracted from preoperative CT improves the prediction of survival. Both the portal and arterial phases should be considered. Radiomic and clinical data are complementary and achieve a preoperative estimation of prognosis equivalent to that achieved in the postoperative setting.

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.

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.

The continuous improvement of digital assistance in the radiation oncologist's work: from web-based nomograms to the adoption of large-language models (LLMs). A systematic review by the young group of the Italian association of radiotherapy and clinical oncology (AIRO).

PURPOSE: Recently, the availability of online medical resources for radiation oncologists and trainees has significantly expanded, alongside the development of numerous artificial intelligence (AI)-based tools. This review evaluates the impact of web-based clinical decision-making tools in the clinical practice of radiation oncology. MATERIAL AND METHODS: We searched databases, including PubMed, EMBASE, and Scopus, using keywords related to web-based clinical decision-making tools and radiation oncology, adhering to PRISMA guidelines. RESULTS: Out of 2161 identified manuscripts, 70 were ultimately included in our study. These papers all supported the evidence that web-based tools can be transversally integrated into multiple radiation oncology fields, with online applications available for dose and clinical calculations, staging and other multipurpose intents. Specifically, the possible benefit of web-based nomograms for educational purposes was investigated in 35 of the evaluated manuscripts. As regards to the applications of digital and AI-based tools to treatment planning, diagnosis, treatment strategy selection and follow-up adoption, a total of 35 articles were selected. More specifically, 19 articles investigated the role of these tools in heterogeneous cancer types, while nine and seven articles were related to breast and head & neck cancers, respectively. CONCLUSIONS: Our analysis suggests that employing web-based and AI tools offers promising potential to enhance the personalization of cancer treatment.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

A multicentric study of radiomics and artificial intelligence analysis on contrast-enhanced mammography to identify different histotypes of breast cancer.

OBJECTIVE: To evaluate the performance of radiomic analysis on contrast-enhanced mammography images to identify different histotypes of breast cancer mainly in order to predict grading, to identify hormone receptors, to discriminate human epidermal growth factor receptor 2 (HER2) and to identify luminal histotype of the breast cancer. METHODS: From four Italian centers were recruited 180 malignant lesions and 68 benign lesions. However, only the malignant lesions were considered for the analysis. All patients underwent contrast-enhanced mammography in cranium caudal (CC) and medium lateral oblique (MLO) view. Considering histological findings as the ground truth, four outcomes were considered: (1) G1 + G2 vs. G3; (2) HER2 + vs. HER2 - ; (3) HR + vs. HR - ; and (4) non-luminal vs. luminal A or HR + /HER2- and luminal B or HR + /HER2 + . For multivariate analysis feature selection, balancing techniques and patter recognition approaches were considered. RESULTS: The univariate findings showed that the diagnostic performance is low for each outcome, while the results of the multivariate analysis showed that better performances can be obtained. In the HER2 + detection, the best performance (73% of accuracy and AUC = 0.77) was obtained using a linear regression model (LRM) with 12 features extracted by MLO view. In the HR + detection, the best performance (77% of accuracy and AUC = 0.80) was obtained using a LRM with 14 features extracted by MLO view. In grading classification, the best performance was obtained by a decision tree trained with three predictors extracted by MLO view reaching an accuracy of 82% on validation set. In the luminal versus non-luminal histotype classification, the best performance was obtained by a bagged tree trained with 15 predictors extracted by CC view reaching an accuracy of 94% on validation set. CONCLUSIONS: The results suggest that radiomics analysis can be effectively applied to design a tool to support physician decision making in breast cancer classification. In particular, the classification of luminal versus non-luminal histotypes can be performed with high accuracy.

Lung cancer multi-omics digital human avatars for integrating precision medicine into clinical practice: the LANTERN study.

BACKGROUND: The current management of lung cancer patients has reached a high level of complexity. Indeed, besides the traditional clinical variables (e.g., age, sex, TNM stage), new omics data have recently been introduced in clinical practice, thereby making more complex the decision-making process. With the advent of Artificial intelligence (AI) techniques, various omics datasets may be used to create more accurate predictive models paving the way for a better care in lung cancer patients. METHODS: The LANTERN study is a multi-center observational clinical trial involving a multidisciplinary consortium of five institutions from different European countries. The aim of this trial is to develop accurate several predictive models for lung cancer patients, through the creation of Digital Human Avatars (DHA), defined as digital representations of patients using various omics-based variables and integrating well-established clinical factors with genomic data, quantitative imaging data etc. A total of 600 lung cancer patients will be prospectively enrolled by the recruiting centers and multi-omics data will be collected. Data will then be modelled and parameterized in an experimental context of cutting-edge big data analysis. All data variables will be recorded according to a shared common ontology based on variable-specific domains in order to enhance their direct actionability. An exploratory analysis will then initiate the biomarker identification process. The second phase of the project will focus on creating multiple multivariate models trained though advanced machine learning (ML) and AI techniques for the specific areas of interest. Finally, the developed models will be validated in order to test their robustness, transferability and generalizability, leading to the development of the DHA. All the potential clinical and scientific stakeholders will be involved in the DHA development process. The main goals aim of LANTERN project are: i) To develop predictive models for lung cancer diagnosis and histological characterization; (ii) to set up personalized predictive models for individual-specific treatments; iii) to enable feedback data loops for preventive healthcare strategies and quality of life management. DISCUSSION: The LANTERN project will develop a predictive platform based on integration of multi-omics data. This will enhance the generation of important and valuable information assets, in order to identify new biomarkers that can be used for early detection, improved tumor diagnosis and personalization of treatment protocols. ETHICS COMMITTEE APPROVAL NUMBER: 5420 - 0002485/23 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore Ethics Committee. TRIAL REGISTRATION: clinicaltrial.gov - NCT05802771.

Radiomics systematic review in cervical cancer: gynecological oncologists' perspective.

OBJECTIVE: Radiomics is the process of extracting quantitative features from radiological images, and represents a relatively new field in gynecological cancers. Cervical cancer has been the most studied gynecological tumor for what concerns radiomics analysis. The aim of this study was to report on the clinical applications of radiomics combined and/or compared with clinical-pathological variables in patients with cervical cancer. METHODS: A systematic review of the literature from inception to February 2023 was performed, including studies on cervical cancer analysing a predictive/prognostic radiomics model, which was combined and/or compared with a radiological or a clinical-pathological model. RESULTS: A total of 57 of 334 (17.1%) screened studies met inclusion criteria. The majority of studies used magnetic resonance imaging (MRI), but positron emission tomography (PET)/computed tomography (CT) scan, CT scan, and ultrasound scan also underwent radiomics analysis. In apparent early-stage disease, the majority of studies (16/27, 59.3%) analysed the role of radiomics signature in predicting lymph node metastasis; six (22.2%) investigated the prediction of radiomics to detect lymphovascular space involvement, one (3.7%) investigated depth of stromal infiltration, and one investigated (3.7%) parametrial infiltration. Survival prediction was evaluated both in early-stage and locally advanced settings. No study focused on the application of radiomics in metastatic or recurrent disease. CONCLUSION: Radiomics signatures were predictive of pathological and oncological outcomes, particularly if combined with clinical variables. These may be integrated in a model using different clinical-pathological and translational characteristics, with the aim to tailor and personalize the treatment of each patient with cervical cancer.

Are you planning to be a radiation oncologist? A survey by the young group of the Italian Association of Radiotherapy and Clinical Oncology (yAIRO).

BACKGROUND AND PURPOSE: The Young Section of the Italian Association of Radiotherapy and Clinical Oncology (yAIRO) circulated an online questionnaire survey among residents currently enrolled within Italian radiotherapy residency schools to investigate the profiles, motivations, knowledge of the radiotherapy discipline, organizations and the needs of younger members. MATERIALS AND METHODS: The survey was developed by the yAIRO steering committee and included questions about the demographic characteristics of the residents (Profile A), the background of their clinical experience during the school of medicine and national residency admission test performance (Profile B) and the residents' knowledge of the scientific associations active in the field of radiotherapy (Profile C). RESULTS: Out of 400 residents actually in training, 134 responded to the questionnaire (response rate 33.5%). According to most of the residents, radiotherapy was not adequately studied during the medical school (n. 95; 71%) and an Internship in Radiotherapy was not mandatory (n. 99; 74%). Only a minority of the residents had chosen to complete a master's degree thesis in radiotherapy (n. 12; 9%). A low percentage of the residents stated that they were aware of the Italian Association of Radiotherapy and Clinical Oncology (AIRO), its young section (yAIRO) and the European Society for Radiotherapy and Oncology (ESTRO) when they were in School of Medicine (respectively, 11%, 7% and 13%). CONCLUSIONS: The results of the survey require a profound reflection on the current teaching methods of Radiation Oncology in our country, highlighting the need for a better integration in the framework of the School of Medicine core curriculum.

Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) for oligometastatic patients: a single-center experience.

PURPOSE: Stereotactic body radiotherapy is increasingly used for the treatment of oligometastatic disease. Magnetic resonance-guided stereotactic radiotherapy (MRgSBRT) offers the opportunity to perform dose escalation protocols while reducing the unnecessary irradiation of the surrounding organs at risk. The aim of this retrospective, monoinstitutional study is to evaluate the feasibility and clinical benefit (CB) of MRgSBRT in the setting of oligometastatic patients. MATERIALS AND METHODS: Data from oligometastatic patients treated with MRgSBRT were collected. The primary objectives were to define the 12-month progression-free survival (PFS) and local progression-free survival (LPFS) and 24-month overall survival (OS) rate. The objective response rate (ORR) included complete response (CR) and partial response (PR). CB was defined as the achievement of ORR and stable disease (SD). Toxicities were also assessed according to the CTCAE version 5.0 scale. RESULTS: From February 2017 to March 2021, 59 consecutive patients with a total of 80 lesions were treated by MRgSBRT on a 0.35 T hybrid unit. CR and PR as well as SD were observed in 30 (37.5%), 7 (8.75%), and 17 (21.25%) lesions, respectively. Furthermore, CB was evaluated at a rate of 67.5% with an ORR of 46.25%. Median follow-up time was 14 months (range: 3-46 months). The 12-month LPFS and PFS rates were 70% and 23%, while 24-month OS rate was 93%. No acute toxicity was reported, whereas late pulmonary fibrosis G1 was observed in 9 patients (15.25%). CONCLUSION: MRgSBRT was well tolerated by patients with reported low toxicity levels and a satisfying CB.

Radiomics and artificial intelligence analysis by T2-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging to predict Breast Cancer Histological Outcome.

OBJECTIVE: The objective of the study was to evaluate the accuracy of radiomics features obtained by MR images to predict Breast Cancer Histological Outcome. METHODS: A total of 217 patients with malignant lesions were analysed underwent MRI examinations. Considering histological findings as the ground truth, four different types of findings were used in both univariate and multivariate analyses: (1) G1 + G2 vs G3 classification; (2) presence of human epidermal growth factor receptor 2 (HER2 + vs HER2 -); (3) presence of the hormone receptor (HR + vs HR -); and (4) presence of luminal subtypes of breast cancer. RESULTS: The best accuracy for discriminating HER2 + versus HER2 - breast cancers was obtained considering nine predictors by early phase T1-weighted subtraction images and a decision tree (accuracy of 88% on validation set). The best accuracy for discriminating HR + versus HR - breast cancers was obtained considering nine predictors by T2-weighted subtraction images and a decision tree (accuracy of 90% on validation set). The best accuracy for discriminating G1 + G2 versus G3 breast cancers was obtained considering 16 predictors by early phase T1-weighted subtraction images in a linear regression model with an accuracy of 75%. The best accuracy for discriminating luminal versus non-luminal breast cancers was obtained considering 27 predictors by early phase T1-weighted subtraction images and a decision tree (accuracy of 94% on validation set). CONCLUSIONS: The combination of radiomics analysis and artificial intelligence techniques could be used to support physician decision-making in prediction of Breast Cancer Histological Outcome.

THUNDER 2: THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. METHODS: Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. DISCUSSION: This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

Local tuning of radiomics-based model for predicting pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

PURPOSE: This study aims to further enhance a validated radiomics-based model for predicting pathologic complete response (pCR) after chemo­radiotherapy in locally advanced rectal cancer (LARC) for use in clinical practice. METHODS: A generalized linear model (GLM) to predict pCR in LARC patients previously trained in Europe and validated with an external inter-continental cohort (59 patients), was first examined with further 88 intercontinental patient datasets to assess its reproducibility; then new radiomics and clinical features, and validation methods were investigated to build a new model for enhancing the pCR prediction for patients admitted to our department. The patients were divided into training group (75%) and validation group (25%) according to their demographic. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to reduce the dimensionality of the extracted features of the training group and select the optimal ones; the performance of the reference GLM and enhanced models was compared through the area under curve (AUC) of the receiver operating characteristics. RESULTS: The value of AUC of the reference model was 0.831 (95% CI, 0.701-0.961), and 0.828 (95% CI, 0.700-0.956) in the original and new validation cohorts, respectively, showing a reproducibility in the applicability of the GLM model. Eight features were found to be significant with LASSO and used to establish an enhanced model. The AUC of the enhanced model of 0.926 (95% CI, 0.859-0.993) for training, and 0.926 (95% CI, 0.767-1.00) for the validation group shows better performance than the reference model. CONCLUSIONS: The GLM model shows good reproducibility in predicting pCR in LARC; the enhanced model has the potential to improve prediction accuracy and may be a candidate in clinical practice.

Role of Peripheral Blood Markers for Detecting Response and Predicting Prognosis in Patients with Non-small-cell Lung Cancer Undergoing Neoadjuvant Therapy and Surgery.

INTRODUCTION: To date, no validated predictors of response before neoadjuvant therapy (NAD) are currently available in locally advanced non-small-cell lung cancer (NSCLC). In this study, different peripheral blood markers were investigated before NAD (pre-NAD) and after NAD/before surgery (post-NAD) to evaluate their influence on the treatment outcomes. METHODS: Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent NAD followed by surgery from January 1996 to December 2019 were considered for this retrospective analysis. The impact of peripheral blood markers on downstaging post-NAD and on overall survival (OS) was evaluated using multivariate logistic and Cox regression models. Time to event analysis was performed by means of Kaplan-Meier survival curves and Log Rank tests at 5 years from surgery. RESULTS: Two hundred and seventy-two consecutive patients were included. Most of the patients had Stage III NSCLC (83.5%). N2 disease was reported in 188 (69.1%) patients. Surgical resection was performed in patients with stable disease or downstaging post-NAD. Nodal downstaging was observed in 80% of clinical N2 (cN2) patients. The median follow-up of the total series was 74 months (range 6-302). Five-year OS in the overall population and in N2 population was 74.6% and 73.5%, respectively. The pre-surgery platelets level (PLT) (p = 0.019) and the variation (pre-NAD/post-NAD) of the neutrophil/lymphocyte ratio (p = 0.024) were identified as independent prognostic factors of OS. The preoperative PLT value (p value = 0.031) was confirmed as the only predictor of NAD response. CONCLUSIONS: The clinical role of peripheral blood markers in locally advanced NSCLC needs to be further investigated. Based on these preliminary results, these factors may be used as auxiliary markers for the prediction of response to neoadjuvant treatment and as prognostic factors for stratification in multimodal approaches.

CT-based radiomics modeling for skull dysmorphology severity and surgical outcome prediction in children with isolated sagittal synostosis: a hypothesis-generating study.

PURPOSE: To investigate the potentialities of radiomic analysis and develop radiomic models to predict the skull dysmorphology severity and post-surgical outcome in children with isolated sagittal synostosis (ISS). MATERIALS AND METHODS: Preoperative high-resolution CT scans of infants with ISS treated with surgical correction were retrospectively reviewed. The sagittal suture (ROI_entire) and its sections (ROI_anterior/central/posterior) were segmented. Radiomic features extracted from ROI_entire were correlated to the scaphocephalic severity, while radiomic features extracted from ROI_anterior/central/posterior were correlated to the post-surgical outcome. Logistic regression models were built from selected radiomic features and validated to predict the scaphocephalic severity and post-surgical outcome. RESULTS: A total of 105 patients were enrolled in this study. The kurtosis was obtained from the feature selection process for both scaphocephalic severity and post-surgical outcome prediction. The model predicting the scaphocephalic severity had an area under the curve (AUC) of the receiver operating characteristic of 0.71 and a positive predictive value of 0.83 for the testing set. The model built for the post-surgical outcome showed an AUC (95% CI) of 0.75 (0.61;0.88) and a negative predictive value (95% CI) of 0.95 (0.84;0.99). CONCLUSION: Our results suggest that radiomics could be useful in quantifying tissue microarchitecture along the mid-suture space and potentially provide relevant biological information about the sutural ossification processes to predict the onset of skull deformities and stratify post-surgical outcome.

Does restaging MRI radiomics analysis improve pathological complete response prediction in rectal cancer patients? A prognostic model development.

PURPOSE: Our study investigated the contribution that the application of radiomics analysis on post-treatment magnetic resonance imaging can add to the assessments performed by an experienced disease-specific multidisciplinary tumor board (MTB) for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This analysis included consecutively retrospective LARC patients who obtained a complete or near-complete response after nCRT and/or a pCR after surgery between January 2010 and September 2019. A three-step radiomics features selection was performed and three models were generated: a radiomics model (rRM), a multidisciplinary tumor board model (yMTB) and a combined model (CM). The predictive performance of models was quantified using the receiver operating characteristic (ROC) curve, evaluating the area under curve (AUC). RESULTS: The analysis involved 144 LARC patients; a total of 232 radiomics features were extracted from the MR images acquired post-nCRT. The yMTB, rRM and CM predicted pCR with an AUC of 0.82, 0.73 and 0.84, respectively. ROC comparison was not significant (p = 0.6) between yMTB and CM. CONCLUSION: Radiomics analysis showed good performance in identifying complete responders, which increased when combined with standard clinical evaluation; this increase was not statistically significant but did improve the prediction of clinical response.

Radiomics-based prediction of two-year clinical outcome in locally advanced cervical cancer patients undergoing neoadjuvant chemoradiotherapy.

PURPOSE: The aim of this study is to determine if radiomics features extracted from staging magnetic resonance (MR) images could predict 2-year long-term clinical outcome in patients with locally advanced cervical cancer (LACC) after neoadjuvant chemoradiotherapy (NACRT). MATERIALS AND METHODS: We retrospectively enrolled patients with LACC diagnosis who underwent NACRT followed by radical surgery in two different institutions. Radiomics features were extracted from pre-treatment 1.5 T T2w MR images. The predictive performance of each feature was quantified in terms of Wilcoxon-Mann-Whitney test. Among the significant features, Pearson correlation coefficient (PCC) was calculated to quantify the correlation among the different predictors. A logistic regression model was calculated considering the two most significant features at the univariate analysis showing the lowest PCC value. The predictive performance of the model created was quantified out using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 175 patients were retrospectively enrolled (142 for the training cohort and 33 for the validation one). 1896 radiomic feature were extracted, 91 of which showed significance (p < 0.05) at the univariate analysis. The radiomic model showing the highest predictive value combined the features calculated starting from the gray level co-occurrence-based features. This model achieved an AUC of 0.73 in the training set and 0.91 in the validation set. CONCLUSIONS: The proposed radiomic model showed promising performances in predicting 2-year overall survival before NACRT. Nevertheless, the observed results should be tested in larger studies with consistent external validation cohorts, to confirm their potential clinical use.