PI3Kγδ inhibition suppresses key disease features in a rat model of asthma.

BACKGROUND: Two isoforms of Phosphoinositide 3-kinase (PI3K), p110γ and p110δ, are predominantly expressed in leukocytes and represent attractive therapeutic targets for the treatment of allergic asthma. The study aim was to assess the impact of administration of an inhaled PI3Kγδ inhibitor (AZD8154) in a rat model of asthma. METHODS: Firstly, we checked that the tool compound, AZD8154, inhibited rat PI3K γ & δ kinases using rat cell-based assays. Subsequently, a time-course study was conducted in a rat model of asthma to assess PI3K activity in the lung and how it is temporally associated with other key transcription pathways and asthma like features of the model. Finally, the impact on lung dosed AZD8154 on target engagement, pathway specificity, airway inflammation and lung function changes was assessed. RESULTS: Data showed that AZD8154 could inhibit rat PI3K γ & δ isoforms and, in a rat model of allergic asthma the PI3K pathway was activated in the lung. Intratracheal administration of AZD8154 caused a dose related suppression PI3K pathway activation (reduction in pAkt) and unlike after budesonide treatment, STAT and NF-κB pathways were not affected by AZD8154. The suppression of the PI3K pathway led to a marked inhibition of airway inflammation and reduction in changes in lung function. CONCLUSION: These data show that a dual PI3Kγδ inhibitor suppress key features of disease in a rat model of asthma to a similar degree as budesonide and indicate that dual PI3Kγδ inhibition may be an effective treatment for people suffering from allergic asthma.

Impaired astrocytic synaptic function by peripheral cholesterol metabolite 27-hydroxycholesterol.

Astrocytes represent the most abundant cell type in the brain, where they play critical roles in synaptic transmission, cognition, and behavior. Recent discoveries show astrocytes are involved in synaptic dysfunction during Alzheimer's disease (AD). AD patients have imbalanced cholesterol metabolism, demonstrated by high levels of side-chain oxidized cholesterol known as 27-hydroxycholesterol (27-OH). Evidence from our laboratory has shown that elevated 27-OH can abolish synaptic connectivity during neuromaturation, but its effect on astrocyte function is currently unclear. Our results suggest that elevated 27-OH decreases the astrocyte function in vivo in Cyp27Tg, a mouse model of brain oxysterol imbalance. Here, we report a downregulation of glutamate transporters in the hippocampus of CYP27Tg mice together with increased GFAP. GLT-1 downregulation was also observed when WT mice were fed with high-cholesterol diets. To study the relationship between astrocytes and neurons, we have developed a 3D co-culture system that allows all the cell types from mice embryos to differentiate in vitro. We report that our 3D co-cultures reproduce the effects of 27-OH observed in 2D neurons and in vivo. Moreover, we found novel degenerative effects in astrocytes that do not appear in 2D cultures, together with the downregulation of glutamate transporters GLT-1 and GLAST. We propose that this transporter dysregulation leads to neuronal hyperexcitability and synaptic dysfunction based on the effects of 27-OH on astrocytes. Taken together, these results report a new mechanism linking oxysterol imbalance in the brain and synaptic dysfunction through effects on astrocyte function.

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.

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.

High-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral response.

RIG-I recognizes viral dsRNA and activates a cell-autonomous antiviral response. Upon stimulation, it triggers a signaling cascade leading to the production of type I and III IFNs. IFNs are secreted and signal to elicit the expression of IFN-stimulated genes, establishing an antiviral state of the cell. The topology of this pathway has been studied intensively, however, its exact dynamics are less understood. Here, we employed electroporation to synchronously activate RIG-I, enabling us to characterize cell-intrinsic innate immune signaling at a high temporal resolution. Employing IFNAR1/IFNLR-deficient cells, we could differentiate primary RIG-I signaling from secondary signaling downstream of the IFN receptors. Based on these data, we developed a comprehensive mathematical model capable of simulating signaling downstream of dsRNA recognition by RIG-I and the feedback and signal amplification by IFN. We further investigated the impact of viral antagonists on signaling dynamics. Our work provides a comprehensive insight into the signaling events that occur early upon virus infection and opens new avenues to study and disentangle the complexity of the host-virus interface.

Stereotactic Body Radiotherapy for Lymph-Nodal Oligometastatic Prostate Cancer: A Multicenter Retrospective Experience.

Background: The favorable role of SBRT for lymph-nodal oligometastases from prostate cancer has been reported by several retrospective and prospective experiences, suggesting a more indolent natural history of disease when compared to patients with bone oligometastases. This retrospective multicenter study evaluates the outcomes of a cohort of patients treated with stereotactic body radiotherapy for lymph-nodal oligometastases. Methods: Inclusion criteria were up to five lymph-nodal oligometastases detected either with Choline-PET or PSMA-PET in patients naïve for ADT or already ongoing with systemic therapy and at least 6 Gy per fraction for SBRT. Only patients with exclusive lymph-nodal disease were included. The primary endpoint of the study was LC; a toxicity assessment was retrospectively performed following CTCAE v4.0. Results: A total of 100 lymph-nodal oligometastases in 69 patients have been treated with SBRT between April 2015 and November 2022. The median age was 73 years (range, 60-85). Oligometastatic disease was mainly detected with Choline-PET in 47 cases, while the remaining were diagnosed using PSMA-PET, with most of the patients treated to a single lymph-nodal metastasis (48/69 cases), two in 14 cases, and three in the remaining cases. The median PSA prior to SBRT was 1.35 ng/mL (range, 0.3-23.7 ng/mL). Patients received SBRT with a median total dose of 35 Gy (range, 30-40 Gy) in a median number of 5 (range, 3-6) fractions. With a median follow-up of 16 months (range, 7-59 months), our LC rates were 95.8% and 86.3% at 1 and 2 years. DPFS rates were 90.4% and 53.4%, respectively, at 1 and 2 years, with nine patients developing a sequential oligometastatic disease treated with a second course of SBRT. Polymetastatic disease-free survival (PMFS) at 1 and 2 years was 98% and 96%. Six patients needed ADT after SBRT for a median time of ADT-free survival of 15 months (range, 6-22 months). The median OS was 16 months (range, 7-59) with 1- and 2-year rates of both 98%. In multivariate analysis, higher LC rates and the use of PSMA-PET were related to improved DPFS rates, and OS was significantly related to a lower incidence of distant progression. No G3 or higher adverse events were reported. Conclusions: In our experience, lymph-nodal SBRT for oligometastatic prostate cancer is a safe and effective option for ADT delay with no severe toxicity.

Stereotactic Radiotherapy in Early-Stage Breast Cancer in Neoadjuvant and Exclusive Settings: A Systematic Review.

INTRODUCTION: Breast cancer (BC) is one of the most common tumors; better screening policies and multidisciplinary approach allow personalized treatment. Radiotherapy (RT) plays a central role in the multimodal approach in BC, and recent evidence has shown the non-inferiority of hypofractionated treatments. The aim of this study was to describe the feasibility and validity of stereotactic RT (SBRT) in BC in a neoadjuvant and exclusive setting. METHODS: A PubMed/MEDLINE and Embase systematic review was conducted to assess the role of radiomics in BC. The search strategy was "breast [All Fields] AND "stereotactic" [All Fields] AND "radiotherapy" [All Fields]" and only original articles referred to BC in humans in the English language were considered. RESULTS: A total of 2,149 studies were obtained using the mentioned search strategy on PubMed and Embase. After the complete selection process, a total of 12 papers were considered eligible for the analysis of the results. SBRT in BC was described in 8 studies regarding neoadjuvant approach and 4 papers regarding exclusive approach. CONCLUSIONS: Relative low toxicity rates, the reduced treatment volumes in the neoadjuvant setting, and the possibility to replace surgery when not feasible in exclusive setting resulted to be main advantages for SBRT in BC. Current evidence shows that both the neoadjuvant and the definitive settings seem to be promising clinical scenarios for SBRT, especially for EBC.

The Added Value of [18F]Choline PET/CT in Low-Risk Prostate Cancer Staging: A Case Report.

In the management of prostate cancer (PCa), correct staging is crucial in order to assess the right therapeutic approach. [18F]Choline PET/CT has been shown to provide more accurate staging information than conventional imaging approaches. The aim of this paper is to provide a real practice demonstration of the impact of [18F]Choline PET/CT on low-risk prostate cancer staging and clinical management. We report a 64-year-old man with biochemical PCa recurrence diagnosis after transurethral resection of the prostate. The patient, after the detection of an increased level of PSA, underwent multi-parametric prostate magnetic resonance imaging (mpMRI) that did not show evidence of disease. The patient was admitted to perform [18F]Choline PET/CT that showed a macroscopic prostate recurrence. Patient underwent photon external beam radiation therapy (EBRT) treatment, and [18F]Choline PET/CT was also used to define treatment volumes. At 3- and 6-month clinical follow-up evaluations, no late toxicity was detected and a significant reduction in PSA value was shown. Therefore, our case highlights the potential usefulness of [18F]Choline PET/CT for the staging of low-risk prostate cancer and its impact on the management and quality of life of such patients. The presented case should urge the scientific community to enhance larger and multicentric studies, assessing more extensively the potential impact of [18F]Choline PET/CT in this clinical scenario.

Covid-19 and radiotherapy: a systematic review after 2 years of pandemic.

Introduction: Following the Covid-19 pandemic spread, changes in clinical practice were necessary to limit the pandemic diffusion. Also, oncological practice has undergone changes with radiotherapy (RT) treatments playing a key role.Although several experiences have been published, the aim of this review is to summarize the current evidence after 2 years of pandemic to provide useful conclusions for clinicians. Methods: A Pubmed/MEDLINE and Embase systematic review was conducted. The search strategy was "Covid AND Radiotherapy" and only original articles in the English language were considered. Results: A total of 2.733 papers were obtained using the mentioned search strategy. After the complete selection process, a total of 281 papers were considered eligible for the analysis of the results. Discussion: RT has played a key role in Covid-19 pandemic as it has proved more resilient than surgery and chemotherapy. The impact of the accelerated use of hypofractionated RT and telemedicine will make these strategies central also in the post-pandemic period.

Increased expression and accumulation of GDF15 in IPF extracellular matrix contribute to fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unmet medical need. It is characterized by formation of scar tissue leading to a progressive and irreversible decline in lung function. IPF is associated with repeated injury, which may alter the composition of the extracellular matrix (ECM). Here, we demonstrate that IPF patient-derived pulmonary ECM drives profibrotic response in normal human lung fibroblasts (NHLF) in a 3D spheroid assay. Next, we reveal distinct alterations in composition of the diseased ECM, identifying potentially novel associations with IPF. Growth differentiation factor 15 (GDF15) was identified among the most significantly upregulated proteins in the IPF lung-derived ECM. In vivo, GDF15 neutralization in a bleomycin-induced lung fibrosis model led to significantly less fibrosis. In vitro, recombinant GDF15 (rGDF15) stimulated α smooth muscle actin (αSMA) expression in NHLF, and this was mediated by the activin receptor-like kinase 5 (ALK5) receptor. Furthermore, in the presence of rGDF15, the migration of NHLF in collagen gel was reduced. In addition, we observed a cell type-dependent effect of GDF15 on the expression of cell senescence markers. Our data suggest that GDF15 mediates lung fibrosis through fibroblast activation and differentiation, implicating a potential direct role of this matrix-associated cytokine in promoting aberrant cell responses in disease.

Heel Spur and Radiotherapy: Case Report and Systematic Literature Review.

Heel spur is a chronic inflammatory condition causing pain and other typical symptoms. Therapeutic recommendations include the use of several drug or orthotic/physical therapies, performed alone or in combination. Surgery is usually reserved for refractory conditions. Radiotherapy has been shown to ensure good clinical outcomes in this clinical setting. A systematic review was performed to describe the feasibility and effectiveness of radiotherapy in the treatment of heel spur, evaluating its role in alleviating pain and consequently ensuring a better quality of life. A case report of 45-year-old patient treated for refractary right hindfoot pain was reported. A single fraction of 6 Gy RT was delivered with symptomatic complete response at 2 months observed. A systematic database search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The systematic review included studies describing heel spur treatment and providing complete information about radiotherapy. Fifteen articles published between 1996 and 2020 were reviewed. Study characteristic analysis resulted in seven prospective randomized studies and eight retrospective studies. Radiotherapy of painful heel spur seems to be safe and effective, with high response rates even at low doses and with an overall favorable toxicity profile. Predictive parameters and modern tailored treatment should be investigated with further studies.

Clinical Validation of a Deep-Learning Segmentation Software in Head and Neck: An Early Analysis in a Developing Radiation Oncology Center.

BACKGROUND: Organs at risk (OARs) delineation is a crucial step of radiotherapy (RT) treatment planning workflow. Time-consuming and inter-observer variability are main issues in manual OAR delineation, mainly in the head and neck (H & N) district. Deep-learning based auto-segmentation is a promising strategy to improve OARs contouring in radiotherapy departments. A comparison of deep-learning-generated auto-contours (AC) with manual contours (MC) was performed by three expert radiation oncologists from a single center. METHODS: Planning computed tomography (CT) scans of patients undergoing RT treatments for H&N cancers were considered. CT scans were processed by Limbus Contour auto-segmentation software, a commercial deep-learning auto-segmentation based software to generate AC. H&N protocol was used to perform AC, with the structure set consisting of bilateral brachial plexus, brain, brainstem, bilateral cochlea, pharyngeal constrictors, eye globes, bilateral lens, mandible, optic chiasm, bilateral optic nerves, oral cavity, bilateral parotids, spinal cord, bilateral submandibular glands, lips and thyroid. Manual revision of OARs was performed according to international consensus guidelines. The AC and MC were compared using the Dice similarity coefficient (DSC) and 95% Hausdorff distance transform (DT). RESULTS: A total of 274 contours obtained by processing CT scans were included in the analysis. The highest values of DSC were obtained for the brain (DSC 1.00), left and right eye globes and the mandible (DSC 0.98). The structures with greater MC editing were optic chiasm, optic nerves and cochleae. CONCLUSIONS: In this preliminary analysis, deep-learning auto-segmentation seems to provide acceptable H&N OAR delineations. For less accurate organs, AC could be considered a starting point for review and manual adjustment. Our results suggest that AC could become a useful time-saving tool to optimize workload and resources in RT departments.

Bullous pemphigoid and radiotherapy: Case report and literature review update.

Bullous pemphigoid (BP) is a common autoimmune bullous disease generally occurring in elderly patients. Itchy and tense blisters on normal skin or erythematous and edematous lesions on the trunk and extremities usually characterize BP. Trigger factors are still unclear while several case reports suggest a potential role of radiotherapy (RT) as BP trigger for disease onset or recrudescence. A review was performed to provide an update of literature. A case report of a patient affected by BP undergoing two radiotherapy courses for a primary breast cancer was also reported. A comprehensive review of the published literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review included studies describing BP and its relationships with RT treatments. A total of 13 articles were reviewed. Studies characteristics analysis resulted in eleven case reports, one case series and one large-scale case- control study. Literature update confirms the existence of a reasonable connection between RT and BP. Case report showed that a multidisciplinary management seems to assure the feasibility of RT in patients affected by BP, not depriving them of standard therapeutic opportunities.

Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2'-O-ribose methyltransferases.

The SARS-CoV-2 infection cycle is a multistage process that relies on functional interactions between the host and the pathogen. Here, we repurposed antiviral drugs against both viral and host enzymes to pharmaceutically block methylation of the viral RNA 2'-O-ribose cap needed for viral immune escape. We find that the host cap 2'-O-ribose methyltransferase MTr1 can compensate for loss of viral NSP16 methyltransferase in facilitating virus replication. Concomitant inhibition of MTr1 and NSP16 efficiently suppresses SARS-CoV-2 replication. Using in silico target-based drug screening, we identify a bispecific MTr1/NSP16 inhibitor with anti-SARS-CoV-2 activity in vitro and in vivo but with unfavorable side effects. We further show antiviral activity of inhibitors that target independent stages of the host SAM cycle providing the methyltransferase co-substrate. In particular, the adenosylhomocysteinase (AHCY) inhibitor DZNep is antiviral in in vitro, in ex vivo, and in a mouse infection model and synergizes with existing COVID-19 treatments. Moreover, DZNep exhibits a strong immunomodulatory effect curbing infection-induced hyperinflammation and reduces lung fibrosis markers ex vivo. Thus, multispecific and metabolic MTase inhibitors constitute yet unexplored treatment options against COVID-19.

New dosimetric parameters to predict ano-rectal toxicity during radiotherapy treatment.

PURPOSE: Radiotherapy is essential in the treatment of locally advanced rectal cancer. Side effects of radiotherapy in the treatment of rectal cancer have a great effect on quality of life. The aim of this retrospective study is to evaluate the correlation between dosimetric parameters and acute toxicity in rectal cancer patients. METHODS: We analyzed the Dose Volume Histogram parameters for both the target structures and the Organs at risk of 89 patients. A dedicated statistical analysis was performed for all the acute toxicities showing a frequency rate higher than 20%. A linear logistic regression model was elaborated using the variable showing the highest level of significance at the univariate analysis. RESULTS: The occurrence of proctitis was significantly correlated with three dosimetric parameters: D98% of low ano-rectum, D98% and Dmean of low ano-rectum wall. A predictive linear logistic regression model reports that the D98% of the wall of the low ano-rectum must be < 38.5 Gy to decrease the rate of proctitis. A general analysis on grade 2 acute toxicity occurrence reported that it was correlated with D98% of low ano rectum. CONCLUSIONS: Two dose constraints were elaborated: D98%<33.5 Gy for low ano rectum to prevent grade 2 acute toxicity and D98%<25 Gy for low ano-rectum wall to prevent proctitis (grade 1 or superior).

The impact of radiomics in diagnosis and staging of pancreatic cancer.

Introduction: Pancreatic cancer (PC) is one of the most aggressive tumours, and better risk stratification among patients is required to provide tailored treatment. The meaning of radiomics and texture analysis as predictive techniques are not already systematically assessed. The aim of this study is to assess the role of radiomics in PC. Methods: A PubMed/MEDLINE and Embase systematic review was conducted to assess the role of radiomics in PC. The search strategy was 'radiomics [All Fields] AND ("pancreas" [MeSH Terms] OR "pancreas" [All Fields] OR "pancreatic" [All Fields])' and only original articles referred to PC in humans in the English language were considered. Results: A total of 123 studies and 183 studies were obtained using the mentioned search strategy on PubMed and Embase, respectively. After the complete selection process, a total of 56 papers were considered eligible for the analysis of the results. Radiomics methods were applied in PC for assessment technical feasibility and reproducibility aspects analysis, risk stratification, biologic or genomic status prediction and treatment response prediction. Discussion: Radiomics seems to be a promising approach to evaluate PC from diagnosis to treatment response prediction. Further and larger studies are required to confirm the role and allowed to include radiomics parameter in a comprehensive decision support system.

Five-Fraction Stereotactic Radiotherapy for Brain Metastases: A Single-Institution Experience on Different Dose Schedules.

INTRODUCTION: The most common intracranial neoplasm diagnosed in adults are brain metastases (BrM). The benefit in terms of clinical control and toxicity for stereotactic radiotherapy (SRT) has been investigated for patients with low load of BrM. AIM: The aim of this single-institution experience was to investigate the best dose schedule for five-fraction SRT (FFSRT). METHODS: A retrospective analysis of patients treated for BrM with different dose schedules of FFSRT was performed. Local control (LC) and clinical outcomes were evaluated with magnetic resonance imaging at 3, 6, and 9 months. Toxicity data were also collected. RESULTS: A total of 41 patients treated from November 2016 to September 2020 were enrolled in the analysis. Non-small cell lung cancer (51.2%) and breast cancer (24.3%) represented the most frequent primitive tumors. Treatment was performed on 5 consecutive days with prescribed dose ranging from 30 to 40 Gy, prescribed to the 95% isodose line that covered at least 98% of the gross tumor volume. Statistically significant differences (p = 0.025) with higher LC rates for dose schedules >6 Gy for fractions. Toxicity rates were not found to be higher than G1. CONCLUSION: The results of this retrospective analysis suggest that FFSRT for BrM seems to be safe and feasible. Our results also underline that a total dose lower than 30 Gy in 5 fractions should not be used due to the expected minor LC.

New fractionations in breast cancer: a dosimetric study of 3D-CRT versus VMAT.

INTRODUCTION: Adjuvant radiation therapy (RT) following primary surgery in women affected by early breast cancer (EBC) plays a central role in reducing local recurrences and overall mortality. The FAST-FORWARD trial recently demonstrated that 1-week hypofractionated adjuvant RT is not inferior to the standard schedule in terms of local relapse, cosmetic outcomes and toxicity. The aim of this in silico study was to evaluate the dosimetric aspects of a 1-week RT course, administered through volumetric modulated arc therapy (VMAT), compared with traditional three-dimensional conformal radiation therapy (3D-CRT) with tangential fields. METHODS: Patients affected by left-side EBC undergoing adjuvant RT were selected. ESTRO guidelines for the clinical target volume (CTV) delineation and FAST-FORWARD protocol for CTV to planning target volume (PTV) margin definition were followed. Total prescribed dose was 26 Gy in five fractions. The homogeneity index (HI) and the global conformity index (GCI) were taken into account for planning and dose distribution optimisation purposes. Both 3D-CRT tangential fields and VMAT plans were generated for each patient. RESULTS: The analysis included 21 patients. PTV coverage comparison between 3D-CRT and VMAT plans showed significant increases for GCI (P < 0.05) in VMAT technique; no statistically significant differences were observed regarding HI. For organs at risks (OAR), statistically significant increases were observed in terms of skin V103% (P < 0.002) and ipsilateral lung V30% (P < 0.05) with 3D-CRT and of heart V5% (P < 0.05) with VMAT technique. CONCLUSIONS: This in silico study showed that both 3D-CRT and VMAT are dosimetrically feasible techniques in the framework of 1-week hypofractionated treatments for left EBC.

Radiofrequency Thermoablation and Hypofractionated Radiotherapy Combined Treatment for Bone Metastases: A Retrospective Study.

INTRODUCTION: Bone metastases (BMs) are the common cause of cancer-related pain, as approximately 45% of cancer patients suffer from bone pain (BP). Radiotherapy (RT) is well established as BP treatment strategy; also, other approaches have been shown to be effective in this setting. Radiofrequency thermoablation (RFA) in a combined strategy with RT appears to be feasible and effective in the treatment of metastatic BP ensuring a better quality of life. Aim of this retrospective study was to describe a case series of patients with painful osteolytic lesions at risk of fracture treated with the RFA-RT combined approach, analyzing local control and pain control as outcomes. METHODS: Data of all patients with BM treated with combined approach in our center from April 2016 to June 2020 were retrospectively analyzed. Patients underwent RFA followed by cementoplasty on the same day and RT in a second phase. RT dose ranged between 30 and 37.5 Gy in 5/10 fractions. BP was evaluated according to the numeric rating scale (NRS), at the beginning of treatment and at 1, 2, 3, 6, 9, and 12 months from the end of combined treatment. RESULTS: A total of 27 patients were treated from April 2016 to June 2020 with RFA-RT combined approach. The large majority of patients underwent stereotactic body radiotherapy (SBRT) (23/27). All patients experienced an NRS value decrease >2 at 1 month and between the first and second months. NRS mean value reached 0 at 3, 6, 9, and 12 months' evaluations. DISCUSSION/CONCLUSION: The results of this retrospective analysis of patients treated with RFA-RT combined approach for BP support its safety and efficacy in terms of pain reduction. SBRT role in this combined approach has to be investigated in randomized trials.