Adaptive Individualized high-dose preoperAtive (AIDA) chemoradiation in high-risk rectal cancer: a phase II trial.

PURPOSE: To evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT). METHODS: The primary endpoint was the pCR rate. Secondary endpoints were the predictive value of 18 F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed 18 F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m2 twice daily orally) was prescribed for the entire treatment duration. RESULTS: Eighteen patients (13 males, 5 females; median age 55 years [range, 41-77 years]) were enrolled in the trial. Patients underwent surgical resection at 8-9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal-Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. 18 F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT. CONCLUSIONS: Our results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate.

A Novel Correction Methodology to Improve the Performance of a Low-Cost Hyperspectral Portable Snapshot Camera.

The development of spectral sensors (SSs) capable of retrieving spectral information have opened new opportunities to improve several environmental and agricultural practices, e.g., crop breeding, plant phenotyping, land use monitoring, and crop classification. The SSs are classified as multispectral and hyperspectral (HS) based on the number of the spectral bands resolved and sampled during data acquisition. Large-scale applications of the HS remain limited due to the cost of this type of technology and the technical difficulties in hyperspectral data processing. Low-cost portable hyperspectral cameras (PHCs) have been progressively developed; however, critical aspects associated with data acquisition and processing, such as the presence of spectral discontinuities, signal jumps, and a high level of background noise, were reported. The aim of this work was to analyze and improve the hyperspectral output of a PHC Senop HSC-2 device by developing a general use methodology. Several signal gaps were identified as falls and jumps across the spectral signatures near 513, 650, and 930 nm, while the dark current signal magnitude and variability associated with instrumental noise showed an increasing trend over time. A data correction pipeline was successfully developed and tested, leading to 99% and 74% reductions in radiance signal jumps identified at 650 and 830 nm, respectively, while the impact of noise on the acquired signal was assessed to be in the range of 10% to 15%. The developed methodology can be effectively applied to other low-cost hyperspectral cameras.

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.

New approaches to improve crop tolerance to biotic and abiotic stresses.

During the last years, a great effort has been dedicated at the development and employment of diverse approaches for achieving more stress-tolerant and climate-flexible crops and sustainable yield increases to meet the food and energy demands of the future. The ongoing climate change is in fact leading to more frequent extreme events with a negative impact on food production, such as increased temperatures, drought, and soil salinization as well as invasive arthropod pests and diseases. In this review, diverse "green strategies" (e.g., chemical priming, root-associated microorganisms), and advanced technologies (e.g., genome editing, high-throughput phenotyping) are described on the basis of the most recent research evidence. Particularly, attention has been focused on the potential use in a context of sustainable and climate-smart agriculture (the so called "next agriculture generation") to improve plant tolerance and resilience to abiotic and biotic stresses. In addition, the gap between the results obtained in controlled experiments and those from application of these technologies in real field conditions (lab to field step) is also discussed.

An Italian survey on "palliative intent" radiotherapy.

Background: The aim of this paper is to provide a comprehensive overview of the scenario on radiotherapy (RT) delivered with palliative intent in Italy. Materials and methods: A structured online questionnaire was submitted to Italian radiation oncologists in order to explore the clinical practice in different areas of palliation, namely: bone, lung, brain, liver, and emergencies suitable to RT. Results: 209 radiation oncologists took part in the study. Stereotactic body irradiation was found to be the preferred technique in lung and liver metastases, whereas 3D conformal RT was registered as the technique of choice for bone and brain metastases. The majority (98%) of participants stated to treat mainly radiotherapy emergencies with 3D conformal RT at doses ranging from 25 to 50 Gy. Re-irradiation is delivered by the majority of respondents, whereas post-treatment follow-up is done only by 51.4% of them. Conclusions: This nationwide study highlights some heterogeneity among Italian radiation oncologists regarding treatment and follow-up of metastatic cancer patients.

Palliative radiotherapy indications during the COVID-19 pandemic and in future complex logistic settings: the NORMALITY model.

INTRODUCTION: The COVID-19 pandemic has challenged healthcare systems worldwide over the last few months, and it continues to do so. Although some restrictions are being removed, it is not certain when the pandemic is going to be definitively over. Pandemics can be seen as a highly complex logistic scenario. From this perspective, some of the indications provided for palliative radiotherapy (PRT) during the COVID-19 pandemic could be maintained in the future in settings that limit the possibility of patients achieving symptom relief by radiotherapy. This paper has two aims: (1) to provide a summary of the indications for PRT during the COVID-19 pandemic; since some indications can differ slightly, and to avoid any possible contradictions, an expert panel composed of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) and the Palliative Care and Supportive Therapies Working Group (AIRO-palliative) voted by consensus on the summary; (2) to introduce a clinical care model for PRT [endorsed by AIRO and by a spontaneous Italian collaborative network for PRT named "La Rete del Sollievo" ("The Net of Relief")]. The proposed model, denoted "No cOmpRoMise on quality of life by pALliative radiotherapy" (NORMALITY), is based on an AIRO-palliative consensus-based list of clinical indications for PRT and on practical suggestions regarding the management of patients potentially suitable for PRT but dealing with highly complex logistics scenarios (similar to the ongoing logistics limits due to COVID-19). MATERIAL AND METHODS: First, a summary of the available literature guidelines for PRT published during the COVID-19 pandemic was prepared. A systematic literature search based on the PRISMA approach was performed to retrieve the available literature reporting guideline indications fully or partially focused on PRT. Tables reporting each addressed clinical presentation and respective literature indications were prepared and distributed into two main groups: palliative emergencies and palliative non-emergencies. These summaries were voted in by consensus by selected members of the AIRO and AIRO-palliative panels. Second, based on the summary for palliative indications during the COVID-19 pandemic, a clinical care model to facilitate recruitment and delivery of PRT to patients in complex logistic scenarios was proposed. The summary tables were critically integrated and shuffled according to clinical presentations and then voted on in a second consensus round. Along with the adapted guideline indications, some methods of performing the first triage of patients and facilitating a teleconsultation preliminary to the first in-person visit were developed. RESULTS: After the revision of 161 documents, 13 papers were selected for analysis. From the papers, 19 clinical presentation items were collected; in total, 61 question items were extracted and voted on (i.e., for each presentation, more than one indication was provided from the literature). Two tables summarizing the PRT indications during the COVID-19 pandemic available from the literature (PRT COVID-19 summary tables) were developed: palliative emergencies and palliative non-emergencies. The consensus of the vote by the AIRO panel for the PRT COVID-19 summary was reached. The PRT COVID-19 summary tables for palliative emergencies and palliative non-emergencies were adapted for clinical presentations possibly associated with patients in complex clinical scenarios other than the COVID-19 pandemic. The two new indication tables (i.e., "Normality model of PRT indications") for both palliative emergencies and palliative non-emergencies were voted on in a second consensus round. The consensus rate was reached and strong. Written forms facilitating two levels of teleconsultation (triage and remote visits) were also developed, both in English and in Italian, to evaluate the patients for possible indications for PRT before scheduling clinical visits. CONCLUSION: We provide a comprehensive summary of the literature guideline indications for PRT during COVID-19 pandemic. We also propose a clinical care model including clinical indications and written forms facilitating two levels of teleconsultation (triage and remote visits) to evaluate the patients for indications of PRT before scheduling clinical visits. The normality model could facilitate the provision of PRT to patients in future complex logistic scenarios.

On the accuracy of bulk synthetic CT for MR-guided online adaptive radiotherapy.

PURPOSE: MR-guided radiotherapy (MRgRT) relies on the daily assignment of a relative electron density (RED) map to allow the fraction specific dose calculation. One approach to assign the RED map consists of segmenting the daily magnetic resonance image into five different density levels and assigning a RED bulk value to each level to generate a synthetic CT (sCT). The aim of this study is to evaluate the dose calculation accuracy of this approach for applications in MRgRT. METHODS: A planning CT (pCT) was acquired for 26 patients with abdominal and pelvic lesions and segmented in five levels similar to an online approach: air, lung, fat, soft tissue and bone. For each patient, the median RED value was calculated for fat, soft tissue and bone. Two sCTs were generated assigning different bulk values to the segmented levels on pCT: The sCTICRU uses the RED values recommended by ICRU46, and the sCTtailor uses the median patient-specific RED values. The same treatment plan was calculated on two the sCTs and the pCT. The dose calculation accuracy was investigated in terms of gamma analysis and dose volume histogram parameters. RESULTS: Good agreement was found between dose calculated on sCTs and pCT (gamma passing rate 1%/1 mm equal to 91.2% ± 6.9% for sCTICRU and 93.7% ± 5.3% b or sCTtailor). The mean difference in estimating V95 (PTV) was equal to 0.2% using sCTtailor and 1.2% using sCTICRU, respect to pCT values CONCLUSIONS: The bulk sCT guarantees a high level of dose calculation accuracy also in presence of magnetic field, making this approach suitable to MRgRT. This accuracy can be improved by using patient-specific RED values.

Adjuvant chemoradiation in pancreatic cancer: impact of radiotherapy dose on survival.

BACKGROUND: To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A multicenter retrospective analysis on 514 patients with PDAC (T1-4; N0-1; M0) treated with surgical resection with macroscopically negative margins (R0-1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. RESULTS: Median follow-up was 35 months (range: 3-120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3-4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3-4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. CONCLUSIONS: Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.

Magnetic resonance imaging (MRI) compared with computed tomography (CT) for interobserver agreement of gross tumor volume delineation in pancreatic cancer: a multi-institutional contouring study on behalf of the AIRO group for gastrointestinal cancers.

BACKGROUND: Due to the high soft tissue resolution, magnetic resonance imaging (MRI) could improve the accuracy of pancreatic tumor delineation in radiation treatment planning. A multi-institutional study was proposed to evaluate the impact of MRI on inter-observer agreement in gross tumor volume (GTV) and duodenum delineation for pancreatic cancer compared with computer tomography (CT). MATERIAL AND METHODS: Two clinical cases of borderline resectable (Case 1) and unresectable (Case 2) pancreatic cancer were selected. In two sequential steps, diagnostic contrast-enhanced CT scan and MRI sequences were sent to the participating centers. CT-GTVs were contoured while blinded to MRI data sets. DICE index was used to evaluate the spatial overlap accuracy. RESULTS: Thirty-one radiation oncologists from different Institutions submitted the delineated volumes. CT- and MRI-GTV mean volumes were 21.6 ± 9.0 cm3 and 17.2 ± 6.0 cm3, respectively for Case 1, and 31.3 ± 15.6 cm3 and 33.2 ± 20.2 cm3, respectively for Case 2. Resulting MRI-GTV mean volume was significantly smaller than CT-GTV in the borderline resectable case (p < .05). A substantial agreement was shown by the median DICE index for CT- and MRI-GTV resulting as 0.74 (IQR: 0.67-0.75) and 0.61 (IQR: 0.57-0.67) for Case 1; a moderate agreement was instead reported for Case 2: 0.59 (IQR:0.52-0.66) and 0.53 (IQR:0.42-0.62) for CT- and MRI-GTV, respectively. CONCLUSION: Diagnostic MRI resulted in smaller GTV in borderline resectable case with a substantial agreement between observers, and was comparable to CT scan in interobserver variability, in both cases. The greater variability in the unresectable case underlines the critical issues related to the outlining when vascular structures are more involved. The integration of MRI with contrast-enhancement CT, thanks to its high definition of tumor relationship with neighboring vessels, could offer a greater accuracy of target delineation.

A new frontier of image guidance: Organs at risk avoidance with MRI-guided respiratory-gated intensity modulated radiotherapy: Technical note and report of a case.

The case of a 50-year-old man affected by a rhabdomiosarcoma metastatic lesion in the left flank Is reported. The patient was addressed to 50.4 Gy radiotherapy with concomitant chemotherapy in order to locally control the lesion. A Tri-60-Co magnetic resonance hybrid radiotherapy unit was used for treatment delivery and a respiratory gating protocol was applied for the different breathing phases (Free Breathing, Deep Inspiration Breath Hold and Final Expiration Breath Hold). Three intensity modulated radiation therapy (IMRT) plans were calculated and Final Expiration Breath Hold plan was finally selected due to the absence of PTV coverage differences and better organs at risk sparing (i.e. kidneys). This case report suggests that organs at risk avoidance with MRI-guided respiratory-gated Radiotherapy is feasible and particularly advantageous whenever sparing the organs at risk is of utmost dosimetric or clinical importance.

Evaluation of a simplified optimizer for MR-guided adaptive RT in case of pancreatic cancer.

PURPOSE: Magnetic resonance-guided adaptive radiotherapy (MRgART) is considered a promising resource for pancreatic cancer, as it allows to online modify the dose distribution according to daily anatomy. This study aims to compare the dosimetric performance of a simplified optimizer implemented on a MR-Linac treatment planning system (TPS) with those obtained using an advanced optimizer implemented on a conventional Linac. METHODS: Twenty patients affected by locally advanced pancreatic cancer (LAPC) were considered. Gross tumor volume (GTV) and surrounding organ at risks (OARs) were contoured on the average 4DCT scan. Planning target volume was generated from GTV by adding an isotropic 3 mm margin and excluding overlap areas with OARs. Treatment plans were generated by using the simple optimizer for the MR-Linac in intensity-modulated radiation therapy (IMRT) and the advanced optimizer for conventional Linac in IMRT and volumetric modulated arc therapy (VMAT) technique. Prescription dose was 40 Gy in five fractions. The dosimetric comparison was performed on target coverage, dosimetric indicators, and low dose diffusion. RESULTS: The simplified optimizer of MR-Linac generated clinically acceptable plans in 80% and optimal plans in 55% of cases. The number of clinically acceptable plans obtained using the advanced optimizer of the conventional Linac with IMRT was the same of MR-Linac, but the percentage of optimal plans was higher (65%). Using the VMAT technique, it is possible to obtain clinically acceptable plan in 95% and optimal plans in 90% of cases. The advanced optimizer combined with VMAT technique ensures higher target dose homogeneity and minor diffusion of low doses, but its actual optimization time is not suitable for MRgART. CONCLUSION: Simplified optimization solutions implemented in the MR-Linac TPS allows to elaborate in most of cases treatment plans dosimetrically comparable with those obtained by using an advanced optimizer. A superior treatment plan quality is possible using the VMAT technique that could represent a breakthrough for the MRgART if the modern advancements will lead to shorter optimization times.

Identification of the most significant magnetic resonance imaging (MRI) radiomic features in oncological patients with vertebral bone marrow metastatic disease: a feasibility study.

OBJECTIVES: Recently, radiomic analysis has gained attention as a valuable instrument for the management of oncological patients. The aim of the study is to isolate which features of magnetic resonance imaging (MRI)-based radiomic analysis have to be considered the most significant predictors of metastasis in oncological patients with spinal bone marrow metastatic disease. MATERIALS AND METHODS: Eight oncological patients (3 lung cancer; 1 prostatic cancer; 1 esophageal cancer; 1 nasopharyngeal cancer; 1 hepatocarcinoma; 1 breast cancer) with pre-radiotherapy MR imaging for a total of 58 dorsal vertebral bodies, 29 metastatic and 29 non-metastatic were included. Each vertebral body was contoured in T1 and T2 weighted images at a radiotherapy delineation console. The obtained data were transferred to an automated data extraction system for morphological, statistical and textural analysis. Eighty-nine features for each lesion in both T1 and T2 images were computed as the median of by-slice values. A Wilcoxon test was applied to the 89 features and the most statistically significant of them underwent to a stepwise feature selection, to find the best performing predictors of metastasis in a logistic regression model. An internal cross-validation via bootstrap was conducted for estimating the model performance in terms of the area under the curve (AUC) of the receiver operating characteristic. RESULTS: Of the 89 textural features tested, 16 were found to differ with statistical significance in the metastatic vs non-metastatic group. The best performing model was constituted by two predictors for T1 and T2 images, namely one morphological feature (center of mass shift) (p value < 0.01) for both datasets and one histogram feature minimum grey level (p value < 0.01) for T1 images and one textural feature (grey-level co-occurrence matrix joint variance (p value < 0.01) for T2 images. The internal cross-validation showed an AUC of 0.8141 (95% CI 0.6854-0.9427) in T1 images and 0.9116 (95% CI 0.8294-0.9937) in T2 images. CONCLUSIONS: The results suggest that MRI-based radiomic analysis on oncological patients with bone marrow metastatic disease is able to differentiate between metastatic and non-metastatic vertebral bodies. The most significant predictors of metastasis were found to be based on T2 sequence and were one morphological and one textural feature.

Delta radiomics for rectal cancer response prediction with hybrid 0.35 T magnetic resonance-guided radiotherapy (MRgRT): a hypothesis-generating study for an innovative personalized medicine approach.

The aim of this study was to evaluate the variation of radiomics features, defined as "delta radiomics", in patients undergoing neoadjuvant radiochemotherapy (RCT) for rectal cancer treated with hybrid magnetic resonance (MR)-guided radiotherapy (MRgRT). The delta radiomics features were then correlated with clinical complete response (cCR) outcome, to investigate their predictive power. A total of 16 patients were enrolled, and 5 patients (31%) showed cCR at restaging examinations. T2*/T1 MR images acquired with a hybrid 0.35 T MRgRT unit were considered for this analysis. An imaging acquisition protocol of 6 MR scans per patient was performed: the first MR was acquired at first simulation (t0) and the remaining ones at fractions 5, 10, 15, 20 and 25. Radiomics features were extracted from the gross tumour volume (GTV), and each feature was correlated with the corresponding delivered dose. The variations of each feature during treatment were quantified, and the ratio between the values calculated at different dose levels and the one extracted at t0 was calculated too. The Wilcoxon-Mann-Whitney test was performed to identify the features whose variation can be predictive of cCR, assessed with a MR acquired 6 weeks after RCT and digital examination. The most predictive feature ratios in cCR prediction were the L_least and glnu ones, calculated at the second week of treatment (22 Gy) with a p value = 0.001. Delta radiomics approach showed promising results and the quantitative analysis of images throughout MRgRT treatment can successfully predict cCR offering an innovative personalized medicine approach to rectal cancer treatment.

Low-dose radiotherapy and concurrent FOLFIRI-bevacizumab: a Phase II study.

AIMS: Low-dose radiation therapy (LDRT) can increase biological efficacy of chemotherapy. This Phase II trial evaluates LDRT plus FOLFIRI-bevacizumab (FOLFIRI-B) in metastatic colorectal cancer. PRIMARY OBJECTIVE: raising the clinical complete response rate from 5 to 25%. SECONDARY OBJECTIVES: toxicity, progression-free survival. Patients underwent 12 FOLFIRI-B cycles plus two daily LDRT fractions (20 cGy/6 h interval) on each cycle. Statistical analysis was planned on 18 patients. RESULTS: Results on 18 patients are reported. Specifically considering irradiated sites: 15/18 patients had a partial (11/18) or complete (4/18) response. Among 11 partial responders, three became a pathological CR after surgery. Grade 3-4 toxicity was recorded in two patients (11.1%). At median follow-up of 30 months (range: 8-50), 7/18 patients progressed in irradiated sites. CONCLUSION: Seven out of 18 patients (38.9%) had clinical or pathological CR in lesions treated with LDRT. Further studies on this newer treatment modality seem justified.

Individually optimized stereotactic radiotherapy for pancreatic head tumors: A planning feasibility study.

AIM: Aim of this study was to perform a planning feasibility analysis of a 3-level dose prescription using an IMRT-SIB technique. BACKGROUND: Radiation therapy of locally advanced pancreatic cancer should administer a minimum dose to the duodenum and a very high dose to the vascular infiltration areas to improve the possibility of a radical resection. MATERIALS AND METHODS: Fifteen patients with pancreatic head adenocarcinoma and vascular involvement were included. The duodenal PTV (PTVd) was defined as the GTV overlapping the duodenal PRV. Vascular CTV (CTVv) was defined as the surface of contact or infiltration between the tumor and vessel plus a 5 mm margin. Vascular PTV (PTVv) was considered as the CTVv plus an anisotropic margin. The tumor PTV (PTVt) was defined as the GTV plus a margin including the PTVv and excluding the PTVd. The following doses were prescribed: 30 Gy (6 Gy/fraction) to PTVd, 37.5 Gy (7.5 Gy/fraction) to PTVt, and 45 Gy (9 Gy/fraction) to PTVv, respectively. Treatment was planned with an IMRT technique. RESULTS: The primary end-point (PTVv Dmean > 90%) was achieved in all patients. PTVv D98% > 90% was achieved in 6 patients (40%). OARs constraints were achieved in all patients. CONCLUSIONS: Although the PTVv D95% > 95% objective was achieved only in 40% of patients, the study showed that in 100% of patients it was possible to administer a strongly differentiated mean/median dose. Prospective trials based on clinical application of this strategy seem to be justified in selected patients without overlap between PTVd and PTVv.

Role of microRNA in response to ionizing radiations: evidences and potential impact on clinical practice for radiotherapy.

MicroRNAs (miRNA) are small, non-coding, RNAs with gene expression regulator roles. As an important class of regulators of many cellular pathways, miRNAs are involved in many signaling pathways and DNA damage repair processes, affecting cellular radiosensitivity. Their role has led to interest in oncological implications to improve treatment results. MiRNAs represent a great opportunity to enhance the efficacy of radiotherapy treatments-they can be used to profile the radioresistance of tumors before radiotherapy, monitor their response throughout the treatment, thus helping to select intensification strategies, and also to define the final response to therapy along with risks of recurrence or metastatization. Even though many interesting studies support such potential, nowadays most studies on patient data are limited to experiments profiling tumor aggressiveness and response to radiotherapy. Moreover many studies report different although not conflicting results on the miRNAs evaluated for each tumor type. Without doubt, the clinical potential of such molecules for radiotherapy is striking and of high interest.

Changes of DNA quality and meat physicochemical properties in bovine supraspinatus muscle during microwave heating.

BACKGROUND: The responses of foods to microwave exposure are usually evaluated only in terms of physicochemical properties, thus undervaluing the importance of DNA in an authentication process by methods based on polymerase chain reaction (PCR). In this study, the time effect of microwave heating on some meat physicochemical properties and DNA quality has been investigated. RESULTS: Cooking loss, instrumental colour, pH and other physicochemical parameters varied significantly during microwave cooking, reaching the lowest/highest values after 2.5 min of cooking. The exposure of meat to microwaves was found to affect characteristically the quality of extracted DNA (i.e. yield, purity and degradation). PCR products of both mitochondrial and nuclear regions were successfully observed in all samples. However, the band for large fragments became progressively fainter as treatment time increased. CONCLUSIONS: Microwave heating caused physicochemical changes in bovine supraspinatus muscle and influenced characteristically the yield and integrity of the extracted DNA, indicating that an accurate DNA quantification and a rational choice of the genes (i.e. mtDNA versus nDNA, fragment size, etc.) to be amplified are fundamental in an authentication process by PCR-based methods.

REPeated mAgnetic resonance Image-guided stereotactic body Radiotherapy (MRIg-reSBRT) for oligometastatic patients: REPAIR, a mono-institutional retrospective study.

BACKGROUND: Oligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification. METHODS: We retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2). RESULTS: Eighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24-50 Gy, mean BEDα/ß10=93), while 41 Gy (range 16-50 Gy, mean BEDα/ß10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1-10 Gy) and 3,7 Gy (range 1,6-8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%. CONCLUSIONS: MRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.

Assessing the effectiveness of palliative radiotherapy for painful bone metastases in low- and middle-income countries: A systematic review.

Palliative radiotherapy (RT) effectively relieves pain in patients with bone metastases (BMs). Furthermore, several clinical trials, in most cases conducted in high-income countries (HICs), proved that single-fraction RT is equally effective compared to multi-fractionated RT. However, the evidence is scarce regarding low/middle-income countries (LMICs), where the diagnosis of BMs could be later and RT techniques less advanced. Therefore, we conducted a systematic literature review to evaluate the efficacy of palliative RT of BMs in the LMIC setting. A literature search was performed independently by two authors on the PubMed, Cochrane and Scopus databases. Overall, 333 records were screened and after the selection process, 11 papers were included in the analysis. Complete pain response rates ranged from 11.5% to 37.1% (median: 22%) for single-fraction RT and from 0% to 35.1% (median: 19%) for multi-fractionated RT. Partial pain response rates ranged from 23.1% to 76.9% (median: 53.8%) for single fraction RT and from 23.8% to 84.6% (median: 65%) for multi-fractionated RT. Four randomized trials compared single-fraction RT with multiple-fraction RT and none of them showed significant differences in terms of pain relief. Our analysis showed that pain response rates after palliative RT recorded in LMIC are like those reported in studies performed in HIC. Even in this setting, RT in single fraction shows comparable pain response rates to multifractional RT.