CONCURRENT USE OF ABEMACICLIB AND RADIOTHERAPY IN METASTATIC BREAST CANCER PATIENTS: A SINGLE CENTRE EXPERIENCE.

INTRODUCTION: There is little evidence regarding the safety and efficacy of the combination of abemaciclib plus radiotherapy (RT). The majority of studies investigated the combination of RT with Palbociclib or Ribociclib reporting that hematological toxicity is common. Given the unique toxicity profile of Abemaciclib with greater gastrointestinal toxicity compared to hematological toxicity, we wanted to evaluate the toxicity of the combination with RT in metastatic breast cancer (BC) patients. METHODS: Patients with histologically proven metastatic or locally advanced BC treated with RT and concurrent Abemaciclib were selected. Toxicity was assessed according to the NCI-CTCAE V4.0. RESULTS: 32 metastatic sites were treated in nineteen patients and analyzed. All patients received Abemaciclib during the RT course. 68% of patients received a full dose of Abemaciclib during RT. 71.9% of patients received a palliative intent (median dose= 30Gy, range= 8-30Gy), 26.3% were treated to 9 oligo-metastatic or oligo-progressive sites of disease with stereotactic body radiotherapy (SBRT) (median dose = 30Gy, range 21-30Gy given in 3-5 fractions Overall the rate of G3 toxicity was 15.7%. The rate of G3 hematological toxicity was 10.6 % (2/19 patients, one G3 neutropenia and one G3 anemia). No patient presented diarrhea, including those treated to RT sites close to the bowel. One patient developed G3 skin toxicity. Pain significantly improved after RT (mean value NRS pre-RT=3.9, SD=3.07; mean value NRS after-RT=0.9, SD= 0.46; p=<0.0001) Conclusion: Abemaciclib and Concomitant RT seem well tolerated showing acceptable toxicity.

Exploring Negated Entites for Named Entity Recognition in Italian Lung Cancer Clinical Reports.

This paper explores the potential of leveraging electronic health records (EHRs) for personalized health research through the application of artificial intelligence (AI) techniques, specifically Named Entity Recognition (NER). By extracting crucial patient information from clinical texts, including diagnoses, medications, symptoms, and lab tests, AI facilitates the rapid identification of relevant data, paving the way for future care paradigms. The study focuses on Non-small cell lung cancer (NSCLC) in Italian clinical notes, introducing a novel set of 29 clinical entities that include both presence or absence (negation) of relevant information associated with NSCLC. Using a state-of-the-art model pretrained on Italian biomedical texts, we achieve promising results (average F1-score of 80.8%), demonstrating the feasibility of employing AI for extracting biomedical information in the Italian language.

Cancer-specific dose and fractionation schedules in stereotactic body radiotherapy for oligometastatic disease: An interim analysis of the EORTC-ESTRO E2-RADIatE OligoCare study.

BACKGROUND AND INTRODUCTION: Optimal dose and fractionation in stereotactic body radiotherapy (SBRT) for oligometastatic cancer patients remain unknown. In this interim analysis of OligoCare, we analyzed factors associated with SBRT dose and fractionation. MATERIALS AND METHODS: Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/ß of 10 Gy for all primaries, and cancer-specific α/ß of 10 Gy for non-small cell lung and colorectal cancer (NSCLC, CRC), 2.5 Gy for breast cancer (BC), or 1.5 Gy for prostate cancer (PC). RESULTS: Of the interim analysis population of 1,099 patients, 999 (99.5 %) fulfilled inclusion criteria and received metastasis-directed SBRT for NSCLC (n = 195; 19.5 %), BC (n = 163; 16.3 %), CRC (n = 184; 18.4 %), or PC (n = 457; 47.5 %). Two thirds of patients were treated for single metastasis. Median number of fractions was 5 (IQR, 3-5) and median dose per fraction was 9.7 (IQR, 7.7-12.4) Gy. The most frequently treated sites were non-vertebral bone (22.8 %), lung (21.0 %), and distant lymph node metastases (19.0 %). On multivariate analysis, the dose varied significantly for primary cancer type (BC: 237.3 Gy BED, PC 300.6 Gy BED, and CRC 84.3 Gy BED), and metastatic sites, with higher doses for lung and liver lesions. CONCLUSION: This real-world analysis suggests that SBRT doses are adjusted to the primary cancers and oligometastasis location. Future analysis will address safety and efficacy of this site- and disease-adapted SBRT fractionation approach (NCT03818503).

Health-related quality of life in men with oligometastatic prostate cancer following metastases-directed stereotactic body radiotherapy: Real-world data from the E2-RADIatE OligoCare cohort.

Objective: To evaluate the impact of metastases-directed stereotactic body radiotherapy (SBRT) on health-related quality of life (HRQoL) in men with oligometastatic prostate cancer (PCa) using real-world data from the OligoCare cohort. Materials and methods: OligoCare is a pragmatic, observational cohort designed to assess the impact of metastases-directed SBRT on patients with oligometastatic disease (OMD). We report an interim analyses of the secondary endpoint HRQoL, assessed using the EORTC QLQ-C30, within six months of metastases-directed SBRT for oligometastatic disease in men with PCa among the first 1600 registered patients. HRQoL data collection was optional within the OligoCare cohort. To compare HRQoL between baseline and first follow-up assessment, a Wilcoxon signed-rank test was used. A multiple linear regression model was used to explore the HRQoL associations with predefined factors. Results: Out of the 1600 registered patients, 658 were treated for oligometastatic PCa, of which 233 had baseline QoL data and 132 patients had both baseline and follow-up HRQoL data. At baseline, most patients had a WHO performance status of 0 or 1 (87 %), were de-novo oligometastatic (79 %), had one metastasis (90 %), and had a good overall global health status (mean 80.81, SD16.11, IQR 75-92). 51 % received hormonal therapy as concomitant systemic treatment. Patients with comorbidities as assessed by the Charlson Comorbidity index had a worse global health status at baseline (-4.88, 95 % CI:-9.35, -0.42). No clinically meaningful significant difference in global health status was observed at first assessment following SBRT (median 3.0 months) compared with baseline (mean difference 2.27, 95 % CI:-1.54, 6.08). Upon evaluating the proportions, meaningful clinically important differences (a 10-point or more difference) was observed in, 17 % and 11 % of the patients reporting deterioration and improvement of global health status, respectively. Conclusion: Metastases-directed stereotactic body radiotherapy had no negative impact on global HRQoL within the first six months after treatment.

Breast Volume Is a Predictor of Higher Heart Dose in Whole-Breast Supine Free-Breathing Volumetric-Modulated Arc Therapy Planning.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose (p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD (p = 0.005, p ≤ 0.001) and mean LAD dose (p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

Preventing Cardiotoxicity in Personalized Breast Irradiation.

BACKGROUND: This study aims to assess the benefit of a deep inspiration breath hold (DIBH) over the standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with the LAD dose. METHODS: Patients with left-sided breast cancer undergoing whole breast radiotherapy with DIBH were analyzed. All patients included in the analysis had plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were used to identify the cut-off point of parameters to predict the LAD maximum dose > 10 Gy and LAD mean dose > 4 Gy, and the areas under the curve (AUCs) were computed. Post-test probability has been performed to evaluate the effect of parameters' combination. RESULTS: One hundred ninety-seven patients were analyzed. The LAD dose was significantly reduced in DIBH plans with the maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs. 4.8 Gy, p ≤ 0.001) and 28.1% (mean value 8.2 Gy vs. 12.8 Gy, p ≤ 0.001) in DIBH plans compared to FB plans. The strongest predictor of the LAD dose (maximum > 10 Gy and mean > 4 Gy) was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume (LAD Dmax > 10 Gy) and lung volume, heart volume, and breast separation (LAD Dmean > 4 Gy). CONCLUSION: The dosimetric advantage of DIBH is clear in all patients and DIBH should always be preferred.

Deep pathomics: A new image-based tool for predicting response to treatment in stage III non-small cell lung cancer.

Despite the advantages offered by personalized treatments, there is presently no way to predict response to chemoradiotherapy in patients with non-small cell lung cancer (NSCLC). In this exploratory study, we investigated the application of deep learning techniques to histological tissue slides (deep pathomics), with the aim of predicting the response to therapy in stage III NSCLC. We evaluated 35 digitalized tissue slides (biopsies or surgical specimens) obtained from patients with stage IIIA or IIIB NSCLC. Patients were classified as responders (12/35, 34.7%) or non-responders (23/35, 65.7%) based on the target volume reduction shown on weekly CT scans performed during chemoradiation treatment. Digital tissue slides were tested by five pre-trained convolutional neural networks (CNNs)-AlexNet, VGG, MobileNet, GoogLeNet, and ResNet-using a leave-two patient-out cross validation approach, and we evaluated the networks' performances. GoogLeNet was globally found to be the best CNN, correctly classifying 8/12 responders and 10/11 non-responders. Moreover, Deep-Pathomics was found to be highly specific (TNr: 90.1) and quite sensitive (TPr: 0.75). Our data showed that AI could surpass the capabilities of all presently available diagnostic systems, supplying additional information beyond that currently obtainable in clinical practice. The ability to predict a patient's response to treatment could guide the development of new and more effective therapeutic AI-based approaches and could therefore be considered an effective and innovative step forward in personalised medicine.

The impact of intensified staging and combined therapies in locally advanced pancreatic cancer: a secondary analysis of prospective studies.

AIM: To investigate the use of comprehensive pre-treatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18FFDG-PET/CT scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies. MATERIALS AND METHODS: This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in chemoradiotherapy combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control (LC), and metastasis-free survival (MFS). RESULTS: Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared to non-resected patients (median PFS, 22.5 mo vs. 9.5 mo, P<0.001; median OS, 38.2 mo vs. 13 mo, P<0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to upfront CRT group (median PFS, 19 mo vs. 9.9 mo, P<0.001; median OS, 19.3 mo vs. 14.6 mo, P<0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI 0.12-1.02, P=0.05), and this data was confirmed at multivariate analysis (95% CI 0.09-0.98, P=0.04). Haematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events. CONCLUSIONS: The use of comprehensive pre-treatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.

[Management of the patient with extensive stage microcytoma. The importance of collaboration between oncology and radiotherapy.] / Gestione del paziente con microcitoma a stadio esteso. L'importanza della collaborazione tra oncologia e radioterapia.

Small cell lung cancer (SCLC) represents one of the most complex challenges in the oncological field, with a very slow advancement in research, contrary to the rapid evolutionary of the disease. For nearly two years, the mainstay of treatment for extensive-stage disease (ES-SCLC) has been the combination of platinum-based chemotherapy and immunotherapy, following the approval of atezolizumab and subsequently durvalumab, based on a modest, but significant improvement in overall survival compared to chemotherapy alone. The poor prognosis after the failure of first-line treatment explains the need to maximize the duration and efficacy of up-front systemic therapies, in particular, the emerging role of radiotherapy, also in ES-SCLC. On 10 November 2022, a meeting concerning the integrated treatment of patients with ES-SCLC was held in Rome and was attended by 12 specialists in oncology and radiotherapy from various centers in Lazio, under the direction of Federico Cappuzzo, Emilio Bria and Sara Ramella. The aim of the meeting was to share their clinical experience and to provide a series of practical indications in order to support physicians in the correct integration between first-line chemo-immunotherapy and radiotherapy treatments in ES-SCLC.

V5 and High Sensitivity Cardiac Troponin T for Early Detection of Cardiac Toxicity During Left Breast Cancer Irradiation.

BACKGROUND/AIM: The high sensitivity cardiac troponin T (Hs-cTnT) is a myocardial damage biomarker that could have a predictive value in patients who undergo radiotherapy for left sided breast cancer. The aim of this study was to evaluate the early effect of left whole breast radiotherapy (WB-RT) on serum Hs-cTnT levels and its correlation with pre-existing factors. PATIENTS AND METHODS: The study was conducted from December 2017 to May 2018. Forty-five patients with early stage left-sided breast cancer who received adjuvant breast hypofractionated RT without prior chemotherapy were included. Serum levels of Hs-cTnT were obtained before, weekly during RT, and within one week after the end of treatment. Considering the physiological variations of serum levels, an increase in Hs-cTnT (∆Hs-cTnT) of more than 30% from the baseline value was chosen as a threshold. The main cardiovascular risk factors were recorded. Dose volume histograms (DVHs) were used to provide a quantitative analysis for the whole heart, left ventricle, and left anterior descending artery (LAD). RESULTS: Twelve of 45 patients (26.6%) showed a ∆Hs-cTnT ≥30%. The maximum Hs-cTnT level was recorded in the last week of treatment. ∆Hs-cTnT was strongly associated with heart V5 (p=0.05) and hypertension (p=0.05). Multivariate analysis confirmed the importance of the heart V5 and correlated with ∆Hs-cTnT. CONCLUSION: The increase in Hs-cTnT serum levels during adjuvant WB-RT suggested a correlation with the cardiac radiation dose in chemotherapy-naive breast cancer patients. A longer follow-up is needed to correlate Hs-cTnT values with cardiac events.

Advances in pre-treatment evaluation of pancreatic ductal adenocarcinoma: a narrative review.

Background and Objective: Despite advances in the multidisciplinary management of pancreatic cancer, overall prognosis remains poor, due to early progression of the disease. There is a need to also take action in staging, to make it increasingly accurate and complete, to define the setting of the therapeutic strategy. This review was planned to update the current status of pre-treatment evaluation for pancreatic cancer. Methods: We conducted an extensive review, including relevant articles dealing with traditional imaging, functional imaging and minimally invasive surgical procedures before treatment for pancreatic cancer. We searched articles written in English only. Data in the PubMed database, published in the period between January 2000 and January 2022, were retrieved. Prospective observational studies, retrospective analyses and meta-analyses were reviewed and analysed. Key Content and Findings: Each imaging modality (endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, positron emission tomography/computed tomography, staging laparoscopy) has its own diagnostic advantages and limitations. The sensitivity, specificity and accuracy for each image set are reported. Data that support the increasing role of neoadjuvant therapy (radiotherapy and chemotherapy) and the meaning of a patient-tailored treatment selection, based on tumour staging, are also discussed. Conclusions: A multimodal pre-treatment workup should be searched as it improves staging accuracy, orienting patients with resectable tumors towards surgery, optimizing patient selection with locally advanced tumors to neoadjuvant or definite therapy and avoiding surgical resection or curative radiotherapy in those with metastatic disease.

BOMB trial: First results of stereotactic radiotherapy to primary breast tumor in metastatic breast cancer patients.

Aim: A prospective dose escalation trial was developed to evaluate the maximum tolerated dose of stereotactic body radiotherapy (SABRT) to primary breast cancer in stage IV disease. The aim of the present report was to describe safety and outcome of the first dose level cohort of patients. Material and methods: Patients with histologically confirmed diagnosis of invasive breast carcinoma (biological immuno-histochemical profile: luminal and/or HER2 positive) and distant metastatic disease not progressing after 6 months of systemic therapy with a tumor CT or 5FDG-PET detectable were deemed eligible. The starting dose was 40 Gy in 5 fractions (level 1) because this dose proved to be safe in previous dose-escalation trial on adjuvant stereotactic body radiotherapy. The maximum dose level was chosen as 45 Gy in 5 fractions. Dose limiting toxicity was any grade 3 or worse toxicity according to CTCAE v.4. Time-to-event Keyboard (TITE-Keyboard) design (Lin and Yuan, Biostatistics 2019) was used to find the maximum tolerated dose (MTD). MTD was the dose of radiotherapy associated with a ≤ 20% rate pre-specified treatment-related dose-limiting toxicity (DLT). Results: To date 10 patients have been treated at the starting dose level. Median age was 80 years (range 50-89). 7 patients had a luminal disease, while 3 patients had an HER2 positive disease. No patient suspended ongoing systemic treatment. No protocol defined DLTs were observed. Grade 2 skin toxicity occurred in 4 patients with diseases located close to or involving the skin. Median follow-up was 13 months and all 10 patients were evaluable for response: 5 achieved a complete response, 3 achieved a partial response and 2 showed a stable disease, all with a clinical benefit (resolution of skin retraction, bleeding and pain). The mean reduction in the sum of the largest diameters of target lesions was of 61.4% (DS=17.0%). Conclusions: SABR to primary breast cancer seems feasible and is associated with symptoms reduction. Continued accrual to this study is needed to confirm the safety and assess the MTD. Clinical trial registration: ClinicalTrials.gov, identifier NCT05229575.

Metastases-directed stereotactic body radiotherapy in combination with targeted therapy or immunotherapy: systematic review and consensus recommendations by the EORTC-ESTRO OligoCare consortium.

Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials.

A predictive model of polymetastatic disease from a multicenter large retrospectIve database on colorectal lung metastases treated with stereotactic ablative radiotherapy: The RED LaIT-SABR study.

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD. The study aims to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients. Methods: This international Ethical Committee approved trial (Prot. Negrar 2019-ZT) involved 23 Centers and 450 lung oligometastatic patients. Primary end-point was time to the polymetastatic conversion (tPMC). Additionally, oligometastases number and cumulative gross tumor volume (cumGTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2-3, and 4-5; cumGTV was dichotomized to the value of 10 cc. Results: The median tPMC in the overall population was 26 months. Population was classified in the following tPMC risk classes: low-risk (1-3 oligometastases and cumGTV ≤ 10 cc) with median tPMC of 35.1 months; intermediate-risk (1-3 oligometastases and cumGTV > 10 cc), with median tPMC of 13.9 months, and high-risk (4-5 oligometastases, any cumGTV) with median tPMC of 9.4 months (p = 0.000). Conclusion: The present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole metastases number is not sufficient to define the OMD since patients defined oligometastatic from a numerical point of view might rapidly progress to PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and toxicity in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution.

Treatment of oropharyngeal squamous cell carcinoma: Is swallowing quality better after TORS or RT?

BACKGROUND AND PURPOSE: To answer an important question regarding the long-term morbidity of two oncological equivalent treatment for oropharyngeal squamous cell carcinoma (OPSCC), namely a comparison of swallowing function results between patients treated with trans-oral robotic surgery (TORS) versus patients treated with radiotherapy (RT). MATERIALS AND METHODS: Studies included patients with OPSCC treated with TORS or RT. Articles reporting complete data on MD Anderson Dysphagia Inventory (MDADI) and comparing the two treatments (TORS vs RT) were included in the meta-analysis. Swallowing assessed with MDADI was the primary outcome, the evaluation with instrumental methods was the secondary aim. RESULTS: Included studies provided a total of 196 OPSCC primarily treated with TORS vs 283 OPSCC primarily treated with RT. The mean difference in MDADI score at the longest follow-up was not significantly different between TORS and RT group (mean difference [MD] -0.52; 95% CI -4.53-3.48; p = 0.80). After treatment, mean composite MDADI scores demonstrated a slight impairment in both groups without reaching a statistical difference compared to the baseline status. DIGEST score and Yale score showed a significantly worse function in both treatment groups at 12-month follow-up compared to baseline status. CONCLUSION: The meta-analysis demonstrates that up-front TORS (+- adjuvant therapy) and up-front RT (+- CT) appear to be equivalent treatments in functional outcomes in T1-T2, N0-2 OPSCC, however, both treatments cause impaired swallowing ability. Clinicians should have a holistic approach and work with patients to develop an individualized nutrition plan and swallowing rehabilitation protocol from diagnosis to post-treatment surveillance.

Protective Role of Natural Compounds under Radiation-Induced Injury.

In recent years, evidence has shown the potential therapeutic effects of different natural compounds for the prevention and treatment of radiotherapy-induced mucositis (RIOM). RIOM represents one of the most frequent side effects associated with anti-neoplastic treatments affecting patients' quality of life and treatment response due to radiation therapy discontinuation. The innate radio-protective ability of natural products obtained from plants is in part due to the numerous antioxidants possessed as a part of their normal secondary metabolic processes. However, oxygen presence is a key point for radiation efficacy on cancer cells. The aim of this review is to describe the most recent evidence on radiation-induced injury and the emerging protective role of natural compounds in preventing and treating this specific damage without compromising treatment efficacy.

A Multimodal Ensemble Driven by Multiobjective Optimisation to Predict Overall Survival in Non-Small-Cell Lung Cancer.

Lung cancer accounts for more deaths worldwide than any other cancer disease. In order to provide patients with the most effective treatment for these aggressive tumours, multimodal learning is emerging as a new and promising field of research that aims to extract complementary information from the data of different modalities for prognostic and predictive purposes. This knowledge could be used to optimise current treatments and maximise their effectiveness. To predict overall survival, in this work, we investigate the use of multimodal learning on the CLARO dataset, which includes CT images and clinical data collected from a cohort of non-small-cell lung cancer patients. Our method allows the identification of the optimal set of classifiers to be included in the ensemble in a late fusion approach. Specifically, after training unimodal models on each modality, it selects the best ensemble by solving a multiobjective optimisation problem that maximises both the recognition performance and the diversity of the predictions. In the ensemble, the labels of each sample are assigned using the majority voting rule. As further validation, we show that the proposed ensemble outperforms the models learning a single modality, obtaining state-of-the-art results on the task at hand.

Early GLS changes detection after chemoradiation in locally advanced non-small cell lung cancer (NSCLC).

PURPOSE: Chemoradiation is the standard treatment in patients with locally advanced non-small-cell lung cancer (LA-NSCLC), and thanks to the recent combination with immunotherapy, median survival has unexpectedly improved. This study aims to evaluate early changes in cardiac function after chemoradiotherapy (CRT) in LA-NSCLC by multimodal use of advanced imaging techniques. MATERIALS AND METHODS: This is a prospective, observational cohort study. At the beginning of combined treatment, screening tests including blood samples, electrocardiogram (ECG), echocardiographic examination (TTE), and cardiac magnetic resonance were performed in all patients with LA-NSCLC. ECG and cardiac marker assays were performed weekly during treatment. ECG and TTE were performed at month 1 (M1) and month 3 (M3) after the end of CRT. RESULTS: This preliminary analysis included thirty-four patients with a mean age of 69.5 years. The median follow-up was 27.8 months. 62% of patients were in stage IIIA. Radiation therapy was delivered with a median total dose of 60 Gy with conventional fractionation. All patients were treated with concurrent CRT, and 65% of cases were platinum-based therapy. Global longitudinal strain (GLS) and ejection fraction (EF) progressively decreased from baseline to M1 and M3. There was a strong correlation between GLS and EF reduction (at M1: p = 0.034; at M3: p = 0.018). Cardiac arrhythmias occurred in eight patients (23.5%) at a mean follow-up of 15.8 months after CRT. CONCLUSIONS: Reduction in GLS is an early sign occurring after the end of CRT for LA-NSCLC. Future studies are needed to identify variables that can increase the risk of cardiac events in this patient population to implement adequate damage prevention strategies.