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Introduction: Radiotherapy-induced xerostomia (RIX) is one of the most common adverse effects of radiotherapy (RT) in head and neck cancer patients (HNC) and a major determinant of survivors' quality of life. The primary objective was to evaluate the reduction of patients' xerostomia symptoms after the utilisation of a sodium-hyaluronate mouthwash compared to a placebo solution. The secondary objectives were to evaluate the improvement of quality of life and to evaluate the patients' satisfaction. Methods: The protocol was approved by the ethical committee (Ref. 50,053/19) and registered at ClinicalTrials.gov (ID: NCT05103124). The study was a double-blind randomised clinical trial (RCT) with a crossover design and was conducted at the Fondazione Policlinico Universitario A. Gemelli, Rome. Results: Thirty-two patients completed the study protocol. Lower values of the modified Xerostomia Questionnaire (XQ) were retrieved when comparing the baseline scores to the ones after the treatment, when compared with placebo (Mann-Whitney U test = 0.01); higher values of patients' satisfaction (Likert scale) and modified XQ were retrieved for the sodium-hyaluronate mouthwash (Mann-Whitney U test = 0.001). Conclusions: This RCT highlights the advantages of treating RIX with the sodium-hyaluronate mouthwash since it seems to be clinically effective in reducing its symptoms, without any reported adverse events. Clinicaltrials: gov: NCT05103124 in 17/10/2021.

Introduction: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat metastatic oligorecurrence and locoregional recurrences but limited evidence/guidance exists in the setting of pelvic re-irradiation. An international Delphi study was performed to develop statements to guide practice regarding patient selection, pre-treatment investigations, treatment planning, delivery and cumulative organs at risk (OARs) constraints. Materials and methods: Forty-one radiation oncologists were invited to participate in three online surveys. In Round 1, information and opinion was sought regarding participants’ practice. Guidance statements were developed using this information and in Round 2 participants were asked to indicate their level of agreement with each statement. Consensus was defined as ≥75% agreement. In Round 3, any statements without consensus were re-presented unmodified, alongside a summary of comments from Round 2. Results: Twenty-three radiation oncologists participated in Round 1 and, of these, 21 (91%) and 22 (96%) completed Rounds 2 and 3 respectively. Twenty-nine of 44 statements (66%) achieved consensus in Round 2. The remaining 15 statements (34%) did not achieve further consensus in Round 3. Consensus was achieved for 10 of 17 statements (59%) regarding patient selection/pre-treatment investigations; 12 of 13 statements (92%) concerning treatment planning and delivery; and 7 of 14 statements (50%) relating to OARs. Lack of agreement remained regarding the minimum time interval between irradiation courses, the number/size of pelvic lesions that can be treated and the most appropriate cumulative OAR constraints. Conclusions: This study has established consensus, where possible, in areas of patient selection, pre-treatment investigations, treatment planning and delivery for pelvic SABR re-irradiation for metastatic oligorecurrence and locoregional recurrences. Further research into this technique is required, especially regarding aspects of p

Aims: The best therapeutic approach for local relapses of previously irradiated prostate cancer (PC) is still not defined. Re-irradiation (Re-I) could offer a chance of cure for highly selected patients, although high quality evidences are lacking. The aim of our study is to provide a literature review on efficacy and safety of Re-I. Methods: Only studies where Re-I field overlaps with previous radiotherapy were considered. To determine 2 and 4 years overall mortality (OM), 2 and 4 years biochemical failure (BF) and pooled acute and late G ≥ 3 toxicities rate, a meta-analysis over single arm study was performed. Results: Thirty-eight studies with 1194 patients were included. Median follow-up from Re-I was 30 months (10–94 months). Brachytherapy (BRT) was the most used Re-I technique (27 studies), followed by Stereotactic Body Radiotherapy (SBRT) (9) and External Beam Radiation Therapy (EBRT) (2). Re-I prescription doses ranged from 19 Gy in single HDR fraction to 145 Gy (interstitial BRT). The pooled 2 and 4 years OM rates were 2.1% (95%CI:1.1–3.7%, P < 0.001) and 12.5% (95%CI:8.1–19.5%; P < 0.001). The pooled 2 years BF rate was 24% (95% CI: 19.1–30.2%, P < 0.001). The pooled 4 years BF was 35.6% (95% CI: 28.7–44.3%, P < 0.001). The pooled result of G ≥ 3 acute toxicity was 1.4% (95%CI: 0.7–3%, P < 0.001). One hundred and three G ≥ 3 late adverse events were reported, with a pooled result of G ≥ 3 late toxicity of 8.7% (95%CI: 5.8–13%, P < 0.001). Conclusions: Re-I of local failures from PC showed promising OM and biochemical control rates with a safe toxicity profile.

Background: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. Patients and Methods: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. Results: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6–6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. Conclusions: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Background: The aim of this study was to evaluate the Masaoka–Koga and the tumor node metastases (TNM) staging system in thymic epithelial tumors (TET) considering possible improvements. Methods: We reviewed the data of 379 patients who underwent surgical resection for TET from 1 January 1985 to 1 January 2018, collecting and classifying the pathological report according to the Masaoka–Koga and the TMN system. The number of involved organs was also considered as a possible prognostic factor and integrated in the two staging systems to verify its impact. Results: Considering the Masaoka–Koga system, 5-and 10-year overall survival (5–10YOS) was 96.4% and 88.9% in stage I, 95% and 89.5% in stage II and 85.4% and 72.8% in stage III (p = 0.01), with overlapping in stage I and stage II curves. Considering the TNM system, 5–10YOS was 95.5% and 88.8% in T1, 84.8% and 70.7% in T2 and 88% and 76.3% in T3 (p = 0.02), with overlapping T2– T3 curves. Including the number of involved structures, in Masaoka–Koga stage III, patients with singular involved organs had a 100% and 76.6% vs. 87.7% 5–10YOS, which was 76.6% in patients with multiple organ infiltration. Considering the TNM, T3 patients with singular involved structures presented a 5–10YOS of 100% vs. 62.5% and 37.5% in patients with multiple organ involvement (p = 0.07). Conclusion: The two staging systems present limitations due to overlapping curves in early Masaoka–Koga stages and in advanced T stages for TNM. The addition of the number of involved organs seems to be a promising factor for the prognosis stratification in these patients.

Aims: Pediatric patients may experience considerable distress during radiotherapy. Combining psychological interventions with standard therapies can reduce the need for sedation. The RADAR Project aims to use a systematic method of recording data that can reveal patients' difficulties and fragility during treatment. In this context, the aim of our study was to investigate the ability of a multidimensional assessment tool (M.A.P.-RT schedule) to predict the need for sedation during radiotherapy. The schedule, which is administered during the first evaluation, was created to collect information on patients and their families in a standardized way. Materials and Methods: The study enrolled pediatric patients (aged 0–18 years or 18–21 with cognitive impairment). Data were collected by means of the M.A.P.-RT module; this explores various thematic areas, and is completed by the radiation oncologist, psychologist and nurse during their first evaluation. Features were selected by means of the Boruta method (random forest classifier), and the totals of the significant partial scores on each subsection of the module were inserted into a logistic model in order to test for their correlation with the use of anesthesia and with the frequency of psychological support. The results of logistic regression (LR) were used to identify the best predictors. The AUC was used to identify the best threshold for the scores in the evaluation. Results: A total of 99 patients were considered for this analysis. The feature that best predicted both the need for anesthesia and the frequency of psychological support was the total score (TS), the AUC of the ROC being 0.9875 for anesthesia and 0.8866 for psychological support. Conclusion: During the first evaluation, the M.A.P.-RT form can predict the need for anesthesia in pediatric patients, and is a potential tool for personalizing therapeutic and management procedures.

Background. Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by protein fibroblast-growth-factor-23 (FGF-23) secreting tumors. Complete tumor resection is the current standard of care for TIO; however, some patients may develop tumor recurrence. Due to the rarity of this paraneoplastic syndrome, the role of radiotherapy is unclear. This case is worth reporting because it adds to our knowledge some insights about the potential role of radiotherapy in this rare condition. Case Presentation. After multidisciplinary consultation, in July 2015, postoperative adjuvant radiotherapy was offered to a 52-year-old man with a multiple recurrent ossifying fibromyxoid tumor in the right frontal sinus causing TIO. The patient had a history of multiple bone fractures and pain since more than 20 years. The tumor had been removed in 2003 for the first time. Subsequent endoscopic resections of the tumor had been performed for recurrences of TIO in May 2012, October 2013, and July 2015. Starting from October 2015, external beam radiotherapy was delivered with a volumetric modulated arc technique to the tumor bed with a daily dose of 2 Gy up to a total dose of 60 Gy. After five years from treatment, the patient is free from local tumor relapse, TIO progression, and radiation-induced side effects. Conclusions. Radiotherapy may provide long-term TIO remission and tumor control, thus being a treatment option in cases where surgery is unfeasible or unsuccessful.

Determining the most appropriate management strategy for patients with large tumor masses is a very challenging issue. Unconventional radiotherapy modalities, such as spatially fractionated radiation therapy (SFRT), are associated with dramatic responses. Recent studies have suggested that systemic immune activation may be triggered by SFRT delivery to primary tumor lesion. This report describes the case of a patient treated with a novel form of immune-sparing partially ablative irradiation (ISPART) for a bulky peritoneal metastasis from renal cell cancer, refractory to anti-PD-1 therapy (nivolumab) as third-line therapy after sequential therapy with sunitinib and cabozantinib. The observed response suggests that there may be a synergistic effect between ISPART and immunotherapy. This case report supports the inclusion of ISPART in patients presenting with bulky lesions treated with checkpoint inhibitors.

Introduction: The possibility of intentionally triggering non targeted effects (NTEs) using spatially fractionated radiotherapy (SFRT) alone or combined with immunotherapy is an intriguing and fascinating area of research. Among different techniques for SFRT, stereotactic body radiotherapy targeting exclusively the central hypoxic segment of bulky tumors, (SBRT-PATHY) might trigger immunogenic cell death more efficiently. This in silico study aims to identify the best possible dosimetric trade-off for prescribing SFRT with volumetric modulated arc (VMAT) based stereotactic radiotherapy (SRT). Material and methods: Eight spherical volumes defined “Gross Tumor Volumes” (GTVs) were generated with diameters of 3–10 cm (with incremental steps of 1 cm), simulating tumor lesions. The inner third part of each GTV (GTVcentral) was selected to simulate the central hypoxic area and a ring structure was derived around it to simulate the tumor periphery (GTVperipheral). Volumetric modulated arc radiation treatment (VMAT) plans were calculated to deliver a single fraction of 10 Gy to each GTVcentral with different dose prescription methods: target mean and isodose driven (40, 50, 60, 70, 80 and 90%). The volume of GTVperipheral receiving less than 2 Gy was recorded as dosimetric performance indicator. Results: 56 possible dosimetric scenarios were analyzed. The largest percentage of GTVperipheral spared from the dose of 2 Gy was achieved with dose prescription methods to the 70% isodose line for lesions smaller than 6 cm (range 42.9–48.4%) and to the target mean for larger ones (range 52.9–64.5%). Conclusions: Optimizing the dose prescription method may reduce the dose to tumor periphery in VMAT-based SFRT, thus potentially sparing tumor infiltrating immune cells. The optimal method may vary according to the size of the lesion. This should be taken into account when designing prospective trials using SFRT.

Background: In recent years, novel radiation therapy techniques have moved clinical practice toward tailored medicine. An essential role is played by the decision support system, which requires a standardization of data collection. The Aim of the Prediction Models In Stereotactic External radiotherapy (PRE.M.I.S.E.) project is the implementation of systems that analyze heterogeneous datasets. This article presents the project design, focusing on brain stereotactic radiotherapy (SRT). Materials & methods: First, raw ontology was defined by exploiting semiformal languages (block and entity relationship diagrams) and the natural language; then, it was transposed in a Case Report Form, creating a storage system. Results: More than 130 brain SRT's variables were selected. The dedicated software Beyond Ontology Awareness (BOA-Web) was set and data collection is ongoing. Conclusion: The PRE.M.I.S.E. project provides standardized data collection for a specific radiation therapy technique, such as SRT. Future aims are: including other centers and validating an extracranial SRT ontology. Lay abstract Radiotherapy moves clinical practice toward tailored medicine, where a decision support system is essential. The Prediction Models In Stereotactic External radiotherapy (PRE.M.I.S.E) project aims to implement a system that can analyze heterogeneous datasets. This article presents the project design for brain stereotactic radiotherapy (SRT). First, a raw ontology, which is a classification system where uniform and nonambiguous definitions represent each variable and all their relationships, was defined by exploiting semiformal and natural language. It was then it was transposed in a case report form, setting a storage system. More than 130 brain SRT's variables were selected. The dedicated software BOA-Web (Beyond Ontology Awareness) was set. PRE.M.I.S.E. provides standardized data collection for SRT. Future aims are: including other centers and validating an extracranial SRT

Cancer care is moving from a disease-focused management toward a patient-centered tailored approach. Multidisciplinary management that aims to define individual, optimal treatment strategies through shared decision making between healthcare professionals and patient is a fundamental aspect of high-quality cancer care and often includes radiation oncology. Advances in technology and radiobiological research allow to deliver ever more tailored radiation treatments in an ever easier and faster way, thus improving the efficacy, safety, and accessibility of radiation therapy. While these changes are improving quality of cancer care, they are also enormously increasing complexity of decision making, thus challenging the ability to deliver quality affordable cancer care. In this review, we provide an updated outline of the role of radiation oncology in the modern multidisciplinary treatment of cancer. Particularly, we focus on the way some developments in key areas of cancer management are challenging multidisciplinary cancer care in the different clinical settings of early, locally advanced, and metastatic disease, thus highlighting some priority areas of research.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common—paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyze available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Introduction: Aim of this study was to investigate the ability of pre-treatment four dimensional computed tomography (4DCT) to capture respiratory-motion observed in thoracic and abdominal lesions during treatment. Treatment motion was acquired using full-treatment cine-MR acquisitions. Results of this analysis were compared to the ability of 30 seconds (s) cine Magnetic Resonance (MR) to estimate the same parameters. Methods: A 4DCT and 30 s cine-MR (ViewRay, USA) were acquired on the simulation day for 7 thoracic and 13 abdominal lesions. Mean amplitude, intra- and inter-fraction amplitude variability, and baseline drift were extracted from the full treatment data acquired by 2D cine-MR, and correlated to the motion on pre-treatment 30 s cine-MR and 4DCT. Using the full treatment data, safety margins on the ITV, necessary to account for all motion variability from 4DCT observed during treatment, were calculated. Mean treatment amplitudes were 2 ± 1 mm and 5 ± 3 mm in the anteroposterior (AP) and craniocaudal (CC) direction, respectively. Differences between mean amplitude during treatment and amplitude on 4DCT or during 30 s cine-MR were not significant, but 30 s cine-MR was more accurate than 4DCT. Intra-fraction amplitude variability was positively correlated with both 30 s cine-MR and 4DCT amplitude. Inter-fraction amplitude variability was minimal. Results: Mean baseline drift over all fractions and patients equalled 1 ± 1 mm in both CC and AP direction, but drifts per fraction up to 16 mm (CC) and 12 mm (AP) were observed. Margins necessary on the ITV ranged from 0 to 8 mm in CC and 0 to 5 mm in AP direction. Neither amplitude on 4DCT nor during 30 s cine MR is correlated to the magnitude of drift or the necessary margins in both directions. Conclusion: Lesions moving with small amplitude show limited amplitude variability throughout treatment, making passive motion management strategies seem adequate. However, other variations such as baseline drifts and shi

Purpose: Aim of this study is to experimental evaluate the impact of a 0.35 T transverse magnetic field on dose distribution in presence of tissue-air and tissue-lung interfaces. Methods: The investigation was carried out using MRIdian (ViewRay, Cleveland, Ohio) and it consisted of comparing experimental measurements performed by Gafchromic EBT3 film dosimetry, to Montecarlo simulations, carried out in the presence and, as well as, the absence of the magnetic field. A preliminary dose calibration was planned on MRIdian, arranging 3 × 3 cm2 film pieces in a water slab phantom and exposing them at different beam-on times, in a dose range equal to 0.1–12.1 Gy. All experimental measurements were then carried out using the calibrated films and delivering one single beam orthogonally to three different phantoms: without inhomogeneity, with an air gap and with a lung inhomogeneity. The dose distributions measured by EBT3 films in presence of magnetic field were compared to those calculated in the presence and, as well as, the absence of the magnetic field, in terms of gamma analysis. A quantification of electron return effect (ERE) was also performed. Results: All the tested plans considering the magnetic field show a gamma-passing rate higher than 98% for 3%/3 mm gamma analysis. In presence of tissue-air interface, the electron return effect causes an over-dosage of +31.9% at the first interface and an under-dosage of −33% at the second interface. The dosimetric variations in presence of tissue-lung interface results to be smaller (+0.8% first interface, −1.3% second interface). Conclusion: The impact of 0.35 T magnetic field is not negligible and it can be effectively modelled by the Montecarlo dose calculation platform available in the MRIdian TPS.

Background: Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) have poor prognosis despite several multimodal approaches. Recently, low-dose fractionated radiotherapy concurrent to the induction chemotherapy (IC-LDRT) has been proposed to further improve the effects of chemotherapy and prognosis. Until now, the predictive value of metabolic response after IC-LDRT has not yet been investigated. Aim: to evaluate whether the early metabolic response, assessed by 18F-fluoro-deoxyglucose positron emission-computed tomography (18F-FDG PET-CT), could predict the prognosis in LA-NSCLC patients treated with a multimodal approach, including IC-LDRT. Methods: Forty-four consecutive patients (35males, mean age: 66 ± 7.8 years) with stage IIIA/IIIB NSCLC were retrospectively evaluated. Forty-four patients underwent IC-LDRT (2 cycles of chemotherapy, 40 cGy twice daily), 26/44 neo-adjuvant chemo-radiotherapy (CCRT: 50.4Gy), and 20/44 surgery. 18F-FDG PET-CT was performed before (baseline), after IC-LDRT (early) and after CCRT (final), applying PET response criteria in solid tumours (PERCIST). Patients with complete/partial metabolic response were classified as responders; patients with stable/progressive disease as non-responders. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meyer analysis; the relationship between clinical factors and survivals were assessed using uni-multivariate regression analysis. Results: Forty-four out of 44, 42/44 and 23/42 patients underwent baseline, early and final PET-CT, respectively. SULpeak of primary tumour and lymph-node significantly (p = 0.004, p = 0.0002, respectively) decreased after IC-LDRT with a further reduction after CCRT (p = 0.0006, p = 0.02, respectively). At early PET-CT, 20/42 (47.6%) patients were classified as responders, 22/42 (52.3%) as non-responders. At final PET-CT, 19/23 patients were classified as responders (12 responders and 7 non-responders at early PET-CT), and 4