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Item does not contain fulltext, BACKGROUND: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). CONCLUSION: The OMEC project has resul

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The clinical management of metastatic melanoma has been changed by BRAF (BRAFi) and MEK inhibitors (MEKi), which represent a standard treatment for BRAF-mutant melanoma. In oligoprogressive melanoma patients with BRAF mutations, target therapy can be combined with loco-regional radiotherapy (RT). However, the association of BRAF/MEK inhibitors and RT needs to be carefully monitored for potential increased toxicity. Despite the availability of some reports regarding the tolerability of RT + target therapy, data on simultaneous RT and BRAFi/MEKi are limited and mostly focused on the BRAFi vemurafenib. Here, we report a series of metastatic melanoma patients who received fractioned RT regimens for oligoprogressive disease in combination with the BRAFi dabrafenib and the MEKi trametinib, which have continued beyond progression. None of the cases developed relevant adverse events while receiving RT or interrupted dabrafenib and trametinib administration. These cases suggest that a long period of dabrafenib/trametinib interruption during radiotherapy for oligoprogressive disease can be avoided. Prospective trials are warranted to assess the efficacy and safety of the contemporary administration of BRAF/MEK inhibitors and radiotherapy for oligoprogressive disease.

In the original article published, the last sentence in the sixth paragraph of the introduction section is incorrect. The correct sentence is “This data, were confirmed also in an Italian phase II study, in which it has been demonstrated that gemcitabine-based chemoradiotherapy was correlated with improved overall survival, especially in pts who are clinically more fit to complete the foreseen treatment schedule (CRT) (Mattiucci et al. 2010)”. The original article has been corrected.

The aim of this analysis was to assess the efficacy of stereotactic body radiotherapy (SBRT) in terms of local control (LC) and progression-free survival (PFS) in patients with lymph node metastases (NMs) from solid tumors. A systematic literature search from the earliest date to July 25th, 2019 was performed following PRISMA guidelines. Papers reporting LC and/or PFS of NMs using SBRT (< 10 fractions) were selected. The clinical outcomes rates were pooled by means of a random or fixed-effect model. Twenty-nine studies were eligible (969 patients: 938 (LC) and 698 (PFS)). LC and PFS results were reported in 28 and 18 papers, respectively. Heterogeneity was observed in terms of patient and treatment characteristics. Pooled 2-year LC reported in 11 studies was 79.3% (95%CI, 72.8%–85.7%) with substantial heterogeneity between studies (Q2 test: p = 0.0083; I2 = 57.9%), while pooled 2-year PFS reported in 8 studies was 35.9% (95%CI, 22.1%–49.7%) with very high heterogeneity between studies (Q2 test: p < 0.0001; I2 = 86.1%). Grade ≥ 3 and Grade 5 toxicity rates were 2.0% and 0.2%, respectively. SBRT of NMs seems to be safe and effective in terms of LC. However, due to the marked heterogeneity of the included series, prospective studies are required.

Objective: The aim of this paper is to provide an update about the current clinical indications of RT in this poorly explored field outside the traditional oncological setting. Materials and Methods: We performed a literature search on the main databases, including PubMed, Scopus and Cochrane from their inception until 31stDecember 2020. An additional manual check of scientific meeting proceedings and books was conducted in order to identify all the potentially useful sources. Only essays published in English have been considered for the purposes of this analysis. The searched items included: "Radiotherapy or Radiation Therapy" and "Benign disorder or Benign disease". Results: We provided a list of current clinical indications for benign disorders based on the latest international surveys available, including major sites: eye, bone, head and neck, skin, brain, heart and peripheral vascular system. Conclusions: Radiotherapy for benign diseases is still a feasible therapeutic strategy, which may allow to treat several invalidating conditions, especially after medical therapies have failed thus avoiding potentially invalidating major surgical procedures. A careful evaluation in selecting the indication is essential and all the choices should be thoroughly discussed with the patients.

Purpose: Hepatocellular carcinoma (HCC) in early stages benefits from local ablative treatments such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). In this context, radiotherapy (RT) has shown promising results but has not been thoroughly evaluated. Magnetic resonance-guided RT (MRgRT) may represent a paradigm shifting improvement in stereotactic body radiotherapy (SBRT) for liver tumors. Methods: We retrospectively evaluated HCC patients treated on a hybrid low-tesla MRgRT unit. A total biologically effective dose (BED) > 100 Gy was delivered in 5 consecutive fractions, respecting the appropriate organs-at-risk constraints. Hybrid MR scans were used for treatment planning and cine MR was used for delivery gating. Patients were followed up for toxicity and treatment–response assessment. Results: Ten patients were enrolled, with a total of 12 lesions. All the lesions were irradiated with no interruptions. Six patients had already performed previous local therapies. Median follow-up after SBRT was 6.5 months (1–25). Two cases of acute toxicity were reported (G ≤ 2 according to CTCAE v4.0). At the time of the analysis, 90% of the population presented local control. Child–Pugh before and after treatment remained unchanged in all but one patient. Conclusion: MRgRT is a feasible and safe option showing favorable toxicity profile for HCC treatment.

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The modern management of esophageal cancer is crucially based on a multidisciplinary and multimodal approach. Radiotherapy is involved in neoadjuvant and adjuvant settings; moreover, it includes radical and palliative treatment intention (with a focus on the use of a stent and its potential integration with radiotherapy). In this review, the above-mentioned settings and approaches will be described. Referring to available international guidelines, the background evidence bases will be reviewed, and the ongoing, more relevant trials will be outlined. Target definitions and radiotherapy doses to administer will be mentioned. Peculiar applications such as brachytherapy (interventional radiation oncology), and data regarding innovative approaches including MRI-guided-RT and radiomic analysis will be reported. A focus on the avoidance of surgery for major clinical responses (particularly for SCC) is detailed.

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.

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Purpose/Objective(s): Stereotactic ablative body radiotherapy (SBRT) for vertebral metastases is a challenging treatment process. Planning automation has recently reported the potential to improve plan quality and increase planning efficiency. We performed a dosimetric evaluation of the new Personalized engine implemented in Pinnacle3 for full planning automation of SBRT spine treatments in terms of plan quality, treatment efficiency, and delivery accuracy. Materials/Methods: The Pinnacle3 treatment planning system was used to reoptimize six patients with spinal metastases, employing two separate automated engines. These two automated engines, the existing Autoplanning and the new Personalized, are both template-based algorithms that employ a wishlist to construct planning goals and an iterative technique to replicate the planning procedure performed by skilled planners. The boost tumor volume (BTV) was defined as the macroscopically visible lesion on RM examination, and the planning target volume (PTV) corresponds with the entire vertebra. Dose was prescribed according to simultaneous integrated boost strategy with BTV and PTV irradiated simultaneously over 3 fractions with a dose of 30 and 21 Gy, respectively. Dose-volume histogram (DVH) metrics and conformance indices were used to compare clinically accepted manual plans (MP) with automated plans developed using both Autoplanning (AP) and Personalized engines (Pers). All plans were evaluated for planning efficiency and dose delivery accuracy. Results: For similar spinal cord sparing, automated plans reported a significant improvement of target coverage and dose conformity. On average, Pers plans increased near-minimal dose D98% by 10.4% and 8.9% and target coverage D95% by 8.0% and by 4.6% for BTV and PTV, respectively. Automated plans provided significantly superior dose conformity and dose contrast by 37%–47% and by 4.6%–5.7% compared with manual plans. Overall planning times were dramatically reduced to about

Locally advanced pancreatic cancer (LAPC) represents a major urgency in oncology. Due to the massive involvement of the peripancreatic vessels, a curative-intent surgery is generally precluded. Historically, LAPC has been an indication for palliative systemic therapy. In recent years, with the introduction of intensive multi-agent chemotherapy regimens and aggressive surgical approaches, the survival of LAPC patients has significantly improved. In this complex and rapidly evolving scenario, the role of radiotherapy is still debated. The use of standard-dose conventional fractionated radiotherapy in LAPC has led to unsatisfactory oncological outcomes. However, technological advances in radiation therapy over recent years have definitively changed this paradigm. The use of ablative doses of radiotherapy, in association with image-guidance, respiratory organ-motion management, and adaptive protocols, has led to unprecedented results in terms of local control and survival. In this overview, principles, clinical applications, and current pitfalls of ablative radiotherapy (ART) as an emerging treatment option for LAPC are discussed.

OBJECTIVE: This review aimed at examining efficacy of interventional radiotherapy (brachytherapy-IRT) alone or combined with external beam radiotherapy (EBRT) in stage I esophageal cancer as exclusive treatment. MATERIALS AND METHODS: A systematic research using PubMed, Scopus, and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. We analyzed only clinical study as full-text publication, reporting on patients with stage I esophageal cancer treated with IRT alone or in combination with other treatments (e.g., EBRT). Conference paper, survey, letter, editorial, book chapter, and review were excluded. Patients who underwent previous surgery were excluded. Time restriction (1990-2018) was applied for years of the publication. RESULTS: Twelve studies have been selected. The number of evaluated patients was 514; the median age was 69 years. In the IRT group, the median: Local control (LC) was 77% (range 63%-100%), disease-free survival (DFS) was 68.4% (range 49%-86.3%), the overall survival (OS) was 60% (range 31%-84%), the cancer specific survival (CSS) was 80% (range 55-100%), and grade 3-4 toxicity range was 0%-26%. CONCLUSIONS: IRT alone or combined to EBRT is an effective and safe treatment option for patients with stage I esophageal cancer. Definitive radiation therapy could be an alternative to surgery in patients with superficial cancer.

Local non-surgical interventional percutaneous ablation represents nowadays an important part of the potential treatment strategies. Although surgical ablation represents the gold standard, in the past decade there was an expansion in the use of non-surgical ablative techniques: Radiofrequency, microwave, laser, cryoablation, irreversible electroporation, and interventional radiotherapy (brachytherapy) in primary as well as secondary liver cancers. With the growing experience in the field, there was implemented a new pillar for cancer treatment, together with surgery, chemotherapy as well as radiotherapy, so-called interventional oncology (IO). To date, there are no published papers regarding a comparative interdisciplinary evaluation of all these non-surgical interventional local ablation therapies. Our paper offers a critical interdisciplinary overview of the treatments in both primary and secondary liver tumors, including from a cost-effective point of view. Furthermore, the present status of education in IO and a comparison of actual economic aspects of the treatments are also provided.

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Background: Palliative antalgic treatments represent an issue for clinical management and a challenge for scientific research. Radiotherapy (RT) plays a central role. Techniques such as stereotactic body radiotherapy (SBRT) were largely investigated in several phase 2 studies with good symptom response, becoming widely adopted. However, evidence from randomized, direct comparison of RT and SBRT is still lacking. Methods/design: The PREST trial was designed as an interventional study without medicinal treatment. It is a phase 3, open-label, multicentric trial randomized 1:1. Inclusion criteria include painful spinal bone metastases presenting with a pain level > 4 (or > 1 if being treated with an analgesic) on the Numeric Rating Scale (NRS); expected intermediate/high prognosis (greater than 6 months) according to the Mizumoto prognostic score; low spine instability neoplastic score (SINS) sores (< 7); magnetic resonance imaging (MRI) assessment of the bulky lesion. Patients will be assigned to either standard conventional radiotherapy involving 4 Gy × 5 fractions (fx) to the whole involved vertebra or SBRT by intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) involving 7 Gy × 3 fx to the whole involved vertebra + 10 Gy × 3 fx on the macroscopic lesion (gross tumor volume (GTV)). In the experimental arm, the GTV will be contoured by registration with baseline MRI. Discussion: The primary endpoint is overall pain reduction, defined in terms of variation between baseline and 3-month evaluation; pain will be measured using the NRS. Secondary endpoints include pain control duration; retreatment rates (after a minimum interval of 1 month); local control assessed with RECIST criteria; symptom progression free survival; progression-free survival; overall survival; and quality of life (at 0, 30, and 90 days). Accrual of 330 lesions is planned. The experimental arm is expected to have an improvement in overall pain response rates of 15% wi

Purpose: To investigate the potential benefits of a hypofractionated radiotherapy boost (HRB) after chemotherapy (CT) and concomitant chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) patients. Primary endpoints were early and late toxicity, local control (LC) and pain-free progression (PFP) assessment. Two-years overall survival (OS), metastasis-free survival (MFS) and disease-free survival (DFS) were secondary endpoints. Materials and methods: Patients (pts) affected by unresectable non-metastatic LAPC, previously treated with CT and CRT in upfront or sandwich setting, were selected for sequential HRB. Total prescribed dose was 30 Gy in 5 fractions (fr) to pancreatic primary lesion. Dose de-escalation was allowed in case of failure in respecting organs at risk constraints. Early and late toxicity were assessed according to CTCAE v.4.0 classification. The Kersh-Hazra scale was used for pain assessment. Local Control, PFP, MFS and DFS were calculated from the date of HRB to the date of relapse or the date of the last follow-up. Results: Thirty-one pts affected by unresectable, non-metastatic LAPC were consecutively enrolled from November 2004 to October 2019. All pts completed the planned HRB. Total delivered dose varied according to duodenal dose constraint: 20 Gy in 5 fr (N: 6; 19.4%), 20 Gy in 4 fr (N: 5; 16.2%), 25 Gy in 5 fr (N: 18; 58.0%) and 30 Gy in 6 fr (N: 2; 6.4%). Early and late toxicity were assessed in all pts: no Grade 3 or 4 acute gastrointestinal toxicity and no late gastrointestinal complications occurred. Median LC was 19 months (range 1–156) and 1- and 2-year PFP were 85% and 62.7%, respectively (median 28 months; range 2–139). According to the Kersh-Hazra scale, four pts had a Grade 3 and four pts had a Grade 1 abdominal pain before HRB. At the last follow-up only 3/31 pts had residual Grade 1 abdominal pain.Median MFS was 18 months (range 1–139). The 2-year OS after HRB was 57.4%, while

Introduction: An education strategy was employed in our department to increase the rate of patients with uncomplicated painful bone metastases undergoing single fractionation radiotherapy (SFRT). The purpose of this report is to analyze the results of this strategy over a 5 year period. Materials and Methods: In January 2015, two meetings were organized in our department. In the first, data from an audit on the current SFRT rate were shown. In the second, evidence of SFRT efficacy in the relief of pain from uncomplicated bone metastases was presented. In addition, during the weekly discussion of clinical cases, the opportunity to use the SFRT was systematically recalled. Using our institutional database, all patients treated with radiotherapy for uncomplicated painful bone metastases in the period between 2014 (year considered as a reference) and 2019 were retrieved. Data regarding treatment date (year), radiotherapy fractionation, and tumor, patients, and radiation oncologists characteristics were collected. Results: A total of 627 patients were included in the analysis. The rate of patients undergoing SFRT increased from 4.0% in 2014 to 63.5% in 2019 (p < 0.001). At multivariable analysis, the delivery of SFRT was significantly correlated with older patients age (>80 years), lung cancer as the primary tumor, treatment prescribed by a radiation oncologist dedicated to palliative treatments, and treatment date (2014 vs 2015–2019). Conclusions: This retrospective single-center analysis showed that a simple but intensive and prolonged departmental education strategy can increase the rate of patients treated with SFRT by nearly 16 times.

Aim: The efficacy of low-dose fractionated radiotherapy (LDFRT) and chemotherapy (CHT) combination has large preclinical but little clinical evidence. Therefore, the aim of this review was to collect and analyze the clinical results of LDRT plus concurrent CHT in patients with advanced cancers. Methods: A systematic literature search was conducted on PubMed using the PRISMA methodology. Only studies based on the combination of LDFRT (< 1 Gy/fraction) and CHT were included. Endpoints of the analysis were tumor response, toxicity, and overall survival, with particular focus on any differences between LDFRT-CHT and CHT alone. Results: Twelve studies (307 patients) fulfilled the selection criteria and were included in this review. Two studies were retrospective, one was a prospective pilot trial, six were phase II studies, two were phase I trials, and one was a phase I/II open label study. No randomized controlled trials were found. Seven out of eight studies comparing clinical response showed higher rates after LDFRT-CHT compared to CHT alone. Three out of four studies comparing survival reported improved results after combined treatment. Three studies compared toxicity of CHT and LDFRT plus CHT, and all of them reported similar adverse events rates. In most cases, toxicity was manageable with only three likely LDFRT-unrelated fatal events (1%), all recorded in the same series on LDFRT plus temozolomide in glioblastoma multiforme patients. Conclusion: None of the analyzed studies provided level I evidence on the clinical impact of LDFRT plus CHT. However, it should be noted that, apart from two small series of breast cancers, all studies reported improved therapeutic outcomes and similar tolerability compared to CHT alone. Systematic Review Registration: www.crd.york.ac.uk/prospero/, identifier CRD42020206639.

The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesen-teric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard de-viation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF proba-bilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45–0.53 and 0.58–0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.

Background: Elderly patients are often excluded from advanced treatments owing to clinical complexity or frailty. Magnetic resonance–guided radiotherapy (MRgRT) represents a new frontier of radiotherapy delivery that can play an important role in the management of these patients. Aim: To assess MRgRT feasibility in elderly patients, describe their compliance with this treatment, and provide a scoring system for elderly patient selection. Methods: Patients aged >75 years were enrolled. No restrictions on tumor site, staging, or treatment intent were applied. Patients underwent joint radiation oncology–geriatrics visits to assess the feasibility of MRgRT and to identify the most significant items (i.e. clinical variables) for the setup of a scoring system. The proposed scoring system was then internally validated on a prospectively enrolled cohort of elderly patients who were candidates for MRgRT. Results: Thirty patients were enrolled between February and March 2018. Their mean age was 81.4 ± 3.4 years (range 75–88). Radiotherapy intent was curative in 26 patients; 14 patients were considered frail at screening tests before radiotherapy. Twelve items were identified as clinically significant for the setup of the MASTER score (MRI-Guided Radiotherapy Selection Elderly Score) score. Validation of the score showed 100% reliability, with no patient discharged after selection. Conclusions: MRgRT appears to be feasible in elderly patients and the MASTER score is proposed to support clinical decision-making in recommending elderly patients for this technology.

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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: palliat