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Texture analysis (TA) can provide quantitative features from medical imaging that can be correlated to clinical endpoints. The challenges relevant to robustness of radiomics features have been analyzed by many researchers, as it seems to be influenced by acquisition and reconstruction protocols. Delta-texture analysis (D-TA), conversely, consist in the analysis of TA feature variations at different acquisition times, usually before and after a therapy. Aim of this study was to investigate the influence of different CT scanners and acquisition parameters in the robustness of TA and D-TA. We scanned a commercial phantom (CIRS model 467, Gammex, Middleton, WI, USA), that is used for the calibration of electron density, two times by varying the disposition of plugs, using three different scanners. After the segmentation, we extracted TA features with LifeX and calculated TA features and D-TA features, defined as the variation of each TA parameters extracted from the same position by varying the plugs with the formula (Y–X)/X. The robustness of TA and D-TA features were then tested with intraclass coefficient correlation (ICC) analysis. The reliability of TA parameters across different scans, with different acquisition parameters and ROI positions has shown poor reliability in 12/37 and moderate reliability in the remaining 25/37, with no parameters showing good reliability. The reliability of D-TA, conversely, showed poor reliability in 10/37 parameters, moderate reliability in 10/37 parameters, and good reliability in 17/37 parameters. The comparison between TA and D-TA ICCs showed a significant difference for the whole group of parameters (p:0.004) and for the subclasses of GLCM parameters (p:0.033), whereas for the other subclasses of matrices (GLRLM, NGLDM, GLZLM, Histogram), the difference was not significant. D-TA features seem to be more robust than TA features. These findings reinforce the potentiality for using D-TA features for early assessment of treatment response and for developing tailored therapies. More work is needed in a clinical setting to confirm the results of the present study.

Head and neck squamous cell carcinomas (HNSCC) constitute the sixth most common malignancy worldwide, with approximately 25–40% of the diagnosed patients older than 70 years. HNSCC patients are often frail and frequently have multiple comorbidities due to their unhealthy lifestyle, and evidence suggests that older patients may receive less aggressive and suboptimal treatment than younger patients with the same disease status. The aim of this review is to depict and summarize the evidence regarding the different strategies that can be used in the clinical management of elderly HNSCC patients. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of clinical approaches in the context of elderly HNSCC.

AimTo assess the role of perilesional edema (PE) in non-small cell lung carcinoma (NSCLC) brain metastases (BM) undergoing radiosurgery (SRS).MethodsThis series includes 46 patients with 1–2 BM treated with SRS, selected out of all patients referred for radiotherapy (RT) for BMs over 5 years (2013 to 2017). Both the PE and gross tumor volume (GTV) were contoured on MRI images, and the PE/GTV ratio and PE + GTV value (TV, total volume) were calculated. Our clinical endpoints were brain recurrence free-survival, divided into local brain control (in field, LBC) and distant brain control (out of field, DBC) and overall survival (OS). We analyzed the role of the previously described volumetric parameters and of known clinical prognosticators (disease specific GPA, DS-GPA; chemotherapy, CHT) with Cox regression analyses.ResultsOnly four patients (9%) developed in-field progression, whereas 10 patients (22%) showed new out-of-field BM and thirty-eight patients died in the follow up (83%). In univariate analysis, both volumetric parameters and clinical parameters were correlated with DBC and OS, whereas we did not find any correlation with LBC. In the multivariate analysis of DBC, the significant parameters were PE/GTV ratio (HR 0.302), sex (HR 0.131), and DS-GPA (HR 0.261). The OS multivariate analysis showed that the only significant parameters were DS-GPA (HR 0.478) and TV (HR: 1.038).ConclusionOur study, although with the limitations of a monocentric retrospective study analyzing a small cohort of patients, suggests the role of PE/GTV ratio for the development of new BMs. TV also seems to be correlated with OS, together with known clinical prognosticators. These findings, if validated in a larger prospective dataset, could help in selecting patients for the most suitable RT modality (or systemic therapy approach).

Introduction This is an observational study and the aim is to evaluate the effect of dietary supplements based on Resveratrol, Lycopene, Vitamin C and Anthocyanins (Ixor ® ) in reducing skin toxicity due to external beam radiotherapy in patients affected by breast cancer. Materials and methods 71 patients were enrolled and they were divided in two different groups: a control group (CG) of 41 patients treated with prophylactic topical therapy based on hyaluronic acid and topical steroid therapy in case of occurrence of radiodermatitis, and a Ixor-Group (IG) of 30 patients treated also with an oral therapy based on Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor ® ) at a dose of 2 tablets/day, starting from 10 days before the radiation treatment until 10 days after the end of treatment. Skin toxicity has been related to PTV, to breast volume that received a radiation dose equal or lower than 107%, included between 107% and 110%, or greater than 110% of the prescribed dose. Moreover it's been studied the relationship between skin toxicity and the chemotherapy schedule used before treatment. We calculated in both groups the percentage of patients who had a skin toxicity of grade 2 or 3 (according to RTOG scale). Absolute risk reduction (ARR), relative risk (RR) and odds ratio (OR) have been calculated for each relationship. Results Control Group (CG) patients with a PTV > 500 ml presented skin toxicity G2 + G3 in 30% of cases, versus 25% of Ixor-Group (IG) [OR 0.77]. In patients with a PTV < 500 ml G2 + G3 toxicity was 0% in the IG compared to 18% in CG (OR 0.23). When Dmax was less than or equal to 107% of the prescribed dose skin toxicity was G2 + G3 in 12.5% in CG, versus 0% in IG (OR 0.73), instead when Dmax was included between 107 and 110% of the prescribed dose, G2 + G3 skin toxicity was 35% in CG and 21% in IG (OR 0.50). In patients undergoing chemotherapy with anthracyclines and taxanes, G2 + G3 toxicity was 27% in CG, against 20% in IG (OR 0.68). Conclusions The protective effect of Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor ® ) is more detected in patients with PTV < 500 ml, when Dmax reaches values lower or equal to 107%, but not exceeding 110% of the prescribed dose, and in patients undergoing adjuvant chemotherapy with anthracyclines and taxanes.

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. 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. 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. 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.

We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodological item able to predict the frequency of complete pathological responses and, consequently, the outcome of patients with locally advanced rectal cancer addressed to neoadjuvant chemoradiotherapy (C-RT) and subsequently, to radical surgery. In particular, we carried out a retrospective analysis including 100 patients with locally advanced rectal adenocarcinoma who received C-RT and then radical surgery in three different oncological institutions between January 2013 and December 2019. Our experimental design was focused on the evaluation of the gross tumor volume (GTV) at baseline and after C-RT by means of MRI, which was contoured on T2, DWI, and ADC sequences. Multiple texture parameters were extracted by using a LifeX Software, while D-TA was calculated as percentage of variations in the two time points. Both univariate and multivariate analysis (logistic regression) were, therefore, carried out in order to correlate the above-mentioned TA parameters with the frequency of pathological responses in the examined patients’ population focusing on the detection of complete pathological response (pCR, with no viable cancer cells: TRG 1) as main statistical endpoint. ROC curves were performed on three different datasets considering that on the 21 patients, only 21% achieved an actual pCR. In our training dataset series, pCR frequency significantly correlated with ADC GLCM-Entropy only, when univariate and binary logistic analysis were performed (AUC for pCR was 0.87). A confirmative binary logistic regression analysis was then repeated in the two remaining validation datasets (AUC for pCR was 0.92 and 0.88, respectively). Overall, these results support the hypothesis that D-TA may have a significant predictive value in detecting the occurrence of pCR in our patient series. If confirmed in prospective and multicenter trials, these results may have a critical role in the selection of patients with locally advanced rectal cancer who may benefit form radical surgery after neoadjuvant chemoradiotherapy.

Immune checkpoint blockade is an emerging anticancer strategy, and Nivolumab is a human mAb to PD-1 that is used in the treatment of a number of different malignancies, including non-small cell lung cancer (NSCLC), kidney cancer, urothelial carcinoma and melanoma. Although the use of Nivolumab prolongs survival in a number of patients, this treatment is hampered by high cost. Therefore, the identification of predictive markers of response to treatment in patients is required. In this context, PD-1/PDL1 blockade antitumor effects occur through the reactivation of a pre-existing immune response, and the efficacy of these effects is strictly associated with the presence of necrosis, hypoxia and inflammation at the tumour sites. It has been indicated that these events can be evaluated by specific assessments using a computed tomography (CT) texture analysis (TA) or radiomics. Therefore, a retrospective study was performed, which aimed to evaluate the potential use of this analysis in the identification of patients with NSCLC who may benefit from Nivolumab treatment. A retrospective analysis was performed of 59 patients with metastatic NSCLC who received Nivolumab treatment between January 2015 and July 2017 at Siena University Hospital (35 patients, training dataset), Catanzaro University Hospital and Reggio Calabria Grand Metropolitan Hospital, Italy (24 patients, validation dataset). Pre- and post-contrast CT sequences were used to contour the gross tumour volume (GTV) of the target lesions prior to Nivolumab treatment. The impact of variations on contouring was analysed using two delineations, which were performed on each patient, and the TA parameters were tested for reliability using the Intraclass Coefficient Correlation method (ICC). All analyses for the current study were performed using LifeX Software©. Imaging, clinical and pathological parameters were correlated with progression free survival and overall survival (OS) using Kaplan Meier analysis. An external validation testing was performed for the TA Score using the validation dataset. A total of 59 patients were included in the analysis of the present study. The reliability ICC analysis of 14 TA parameters indicated a highly reproducibility (ICC >0.70, single measure) in 12 (85%) pre- contrast and 13 (93%) post-contrast exams. A specific cut-off was detected for each of the following parameters: volume (score 1 >36 ml), histogram entropy (score 1 > 1.30), compacity (score 1 <3), gray level co-occurrence matrix (GLCM)-entropy (score 1 >1.80), GLCM-Dissimilarity (score 1 >5) and GLCM-Correlation (score 1<0.54). The global texture score allowed the classification of two subgroups of Low (Score 0-1; 36 patients; 61%) and High Risk patients (Score >1; 23 patients; 39%) that respectively, showed a median OS of 26 (mean +/- SD: 18 +/- 1.98 months; 95% CI 14-21 months) and 5 months (mean +/- SD: 6 +/- 0.99 months; 95% CI: 4-8 months; P=0.002). The current study indicated that TA parameters can identify patients that will benefit from PD-1 blockage by defining the radiological settings that are potentially suggestive of an active immune response. These results require further confirmation in prospective trials.

The aim of the study was to investigate boost volume definition, doses, and delivery techniques for rectal cancer dose intensification. An online survey was made on 25 items (characteristics, simulation, imaging, volumes, doses, planning and treatment). Thirty-eight radiation oncologists joined the study. Twenty-one delivered long-course radiotherapy with dose intensification. Boost volume was delineated on diagnostic magnetic resonance imaging (MRI) in 18 centres (85.7%), and computed tomography (CT) and/or positron emission tomography-CT in 9 (42.8%); 16 centres (76.2%) performed co-registration with CT-simulation. Boost dose was delivered on gross tumor volume in 10 centres (47.6%) and on clinical target volume in 11 (52.4%). The most common total dose was 54-55 Gy (71.4%), with moderate hypofractionation (85.7%). Intensity-modulated radiotherapy (IMRT) was used in all centres, with simultaneous integrated boost in 17 (80.8%) and image-guidance in 18 (85.7%). A high quality of treatment using dose escalation can be inferred by widespread multidisciplinary discussion, MRI-based treatment volume delineation, and radiation delivery relying on IMRT with accurate image-guided radiation therapy protocols.

Aims The Pros-IT CNR project aims to monitor a sample of Italian males ≥18 years of age who have been diagnosed in the participating centers with incident prostate cancer, by analyzing their clinical features, treatment protocols and outcome results in relation to quality of life. Methods Pros-IT CNR is an observational, prospective, multicenter study. The National Research Council (CNR), Neuroscience Institute, Aging Branch (Padua) is the promoting center. Ninety-seven Italian centers located throughout Italy were involved. The field study began in September 1, 2014. Subjects eligible were diagnosed with biopsy-verified prostate cancer, naïve. A sample size of 1500 patients was contemplated. A baseline assessment including anamnestic data, clinical history, risk factors, the initial diagnosis, cancer staging information and quality of life (Italian UCLA Prostate Cancer Index; SF-12 Scale) was completed. Six months after the initial diagnosis, a second assessment evaluating the patient’s health status, the treatment carried out, and the quality of life will be made. A third assessment, evaluating the treatment follow-up and the quality of life, will be made 12 months after the initial diagnosis. The 4th, 5th, 6th and 7th assessments, similar to the third, will be completed 24, 36, 48 and 60 months after the initial diagnosis, respectively, and will include also a Food Frequency Questionnaire and the Physical Activity Scale for the Elderly. Discussion The study will provide information on patients’ quality of life and its variations over time in relation to the treatments received for the prostate cancer.

Lung cancer is the most common cancer in the world. One third of patients with non-small cell lung cancer (NSCLC) are diagnosed with locally or regionally advanced unresectable disease at presentation. Currently, in this stage of disease, a combination of chemotherapy and radiotherapy is the standard treatment approach for patients with good performance status, and concomitant chemo-radiotherapy has demonstrated to be the best therapeutic approach. However, despite improvements in treatment, local tumor control remains suboptimal and distant metastases remain the major site of failure. The diversity of molecular abnormalities in NSCLC may partly contribute to its resistance to therapy. It is therefore widely accepted that one approach to improve the efficacy of cancer therapy is the development of rational combinations of anticancer agents that may exhibit synergistic interactions. The introduction of several biologic agents represents an important advance in the management of NSCLC and some of them have shown to have a synergistic effect when given in combination with radiotherapy and chemotherapy in preclinical and in clinical models. In the present review we discuss the rationale and the feasibility of these combinations and the first results available from clinical trials.