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Electrochemotherapy (ECT) is an emerging therapeutic approach gaining growing interest for its potential immunomodulatory effects in cancer treatment. This narrative review systematically examines the current state of knowledge regarding the interplay between ECT and the immune system. Through an analysis of preclinical and clinical studies, the review highlights ECT capacity to induce immunogenic cell death, activate dendritic cells, release tumor antigens, trigger inflammatory responses, and occasionally manifest systemic effects—the abscopal phenomenon. These mechanisms collectively suggest the ECT potential to influence both local tumor control and immune responses. While implications for clinical practice appear promising, warranting the consideration of ECT as a complementary treatment to immunotherapy, the evidence remains preliminary. Consequently, further research is needed to elucidate the underlying mechanisms, optimize treatment protocols, explore potential synergies, and decipher the parameters influencing the abscopal effect. As the field advances, the integration of ECT’s potential immunomodulatory aspects into clinical practice will need careful evaluation and collaboration among clinical practitioners, researchers, and policymakers.

Brachytherapy (BRT) plays a pivotal role in the treatment of tumors, offering precise radiation therapy directly to the affected area. However, this technique demands extensive training and skills development, posing challenges for widespread adoption and ensuring patient safety. This narrative review explored the utilization of augmented reality (AR) in BRT, seeking to summarize existing evidence, discuss key findings, limitations, and quality of research as well as outline future research directions. The review revealed promising findings regarding the integration of AR in BRT. Studies have suggested the feasibility and potential benefits of AR in education, training, intra-operative guidance, and treatment planning. However, the evidence remains limited and heterogeneous, with most studies in preliminary phases. Standardization, prospective clinical trials, patient-centered outcomes assessment, and cost-effectiveness analysis emerge as critical areas for future research. Augmented reality holds transformative potential for BRT by enhancing precision, safety, and training efficiency. To fully implement these benefits, the field requires standardized protocols, rigorous clinical trials, and in-depth patient-centered investigations. Policy-makers and healthcare providers should closely monitor developments in AR and consider its implementation in clinical practice, contingent and robust evidence, and cost-effectiveness analysis. The pro-active pursuit of evidence-based practices will contribute to optimizing patient care in BRT.

Radiotherapy (RT) and electrochemotherapy (ECT) are established local treatments for cancer. While effective, both therapies have limitations, especially in treating bulky and poorly oxygenated tumors. ECT has emerged as a promising palliative treatment, raising interest in exploring its combination with RT to enhance tumor response. However, the potential benefits and challenges of combining these treatments remain unclear. A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and Cochrane libraries were searched. Studies were screened and selected based on predefined inclusion and exclusion criteria. Ten studies were included, comprising in vitro and in vivo experiments. Different tumor types were treated with ECT alone or in combination with RT. ECT plus RT demonstrated superior tumor response compared to that under single therapies or other combinations, regardless of the cytotoxic agent and RT dose. However, no study demonstrated a clear superadditive effect in cell survival curves, suggesting inconclusive evidence of specific ECT-induced radiosensitization. Toxicity data were limited. In conclusion, the combination of ECT and RT consistently improved tumor response compared to that with individual therapies, supporting the potential benefit of their combination. However, evidence for a specific ECT-induced radiosensitization effect is currently lacking. Additional investigations are necessary to elucidate the potential benefits of this combination therapy.

Simulators have revolutionized medical education and training across various disciplines, offering unique advantages in skill acquisition and performance improvement. In the context of interventional radiation therapy (IRT), simulators have emerged as valuable tools for training healthcare professionals in these complex procedures. This narrative review summarized the available evidence on the use of simulators in IRT training, highlighting their impact on proficiency, engagement, and self-confidence as well as their benefits for medical physicists and radiation therapists. A systematic search was conducted in PubMed, resulting in inclusion of 10 papers published since 2009, with 5 of them published since 2020. Publications originated from centers in USA, Ireland, Switzerland, Canada, and Japan, covering a range of IRT settings, including general, prostate, and cervical IRT. The review demonstrated that simulators provide a controlled and realistic environment for skill acquisition, allowing healthcare professionals to practice procedures, optimize image quality, and enhance technical proficiency. The use of simulators addressed the barriers associated with limited caseload and procedural complexity, ultimately contributing to improved education and IRT training. While cost considerations may exist, simulators offer long-term cost-effective solutions, balancing the potential benefits in improving educational outcomes and patient care. Overall, simulators play a crucial role in IRT training, enhancing the skills and competence of healthcare providers and improving access to quality IRT care worldwide. Future research should focus on evaluating the long-term impact of simulation-based training on clinical outcomes and patient satisfaction, exploring different simulation models and training approaches, and addressing region-specific barriers to optimize the utilization of IRT.

Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005–2018). Survival curves were calculated using the Kaplan–Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, 95%CI 0.34–0.92, p = 0.022) or SBRT (HR: 0.27, 95%CI 0.13–0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, 95%CI 0.28–0.70, p < 0.001) and SBRT (HR: 0.40, 95%CI 0.22–0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT.

BackgroundThe objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT).Materials and methodsThis observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson’s comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed.ResultsA total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/β=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced >G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (> 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox’s regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008).ConclusionsThe unexpected results of this analysis could be explained by a “response shift bias” concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens.

Abstract Background Cancer-induced bone pain (CIBP), caused by bone metastases, is a common complication of cancer and strongly impairs quality of life (QoL). External beam radiotherapy (EBRT) is the current standard of care for treatment of CIBP. However, approximately 45% of patients have no adequate pain response after EBRT. Magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) may improve pain palliation in this patient population. The main objective of this trial was to compare MR-HIFU, EBRT, and MR-HIFU + EBRT for the palliative treatment of bone metastases. Methods/design The FURTHER trial is an international multicenter, three-armed randomized controlled trial. A total of 216 patients with painful bone metastases will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or combined treatment with EBRT followed by MR-HIFU. During a follow-up period of 6 months, patients will be contacted at eight time points to retrieve information about their level of pain, QoL, and the occurrence of (serious) adverse events. The primary outcome of the trial is pain response at 14 days after start of treatment. Secondary outcomes include pain response at 14 days after trial enrolment, pain scores (daily until the 21st day and at 4, 6, 12 and 24 weeks), toxicity, adverse events, QoL, and survival. Cost-effectiveness and cost-utility analysis will be conducted. Discussion The FURTHER trial aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU—alone or in combination with EBRT—compared to EBRT to relieve CIBP. The trial will be performed in six hospitals in four European countries, all of which are partners in the FURTHER consortium. Trial registration The FURTHER trial is registered under the Netherlands Trials Register number NL71303.041.19 and ClinicalTrials.gov registration number NCT04307914. Date of trial registration is 13–01-2020.

Abstract Previous trials showed the tolerability and efficacy of a palliative radiotherapy (RT) regimen (SHARON) based on the 4 fractions delivered in 2 days in different oncological settings. In order to identify possible predictors of symptomatic response, the purpose of this study is to perform a pooled analysis of previous trials. We analyzed the impact on symptomatic response of the following parameters: tumor site, histological type, performance status (ECOG), dominant symptom, and RT dose using the Chi-square test and Fisher’s exact test. One-hundred-eighty patients were analyzed. Median RT dose was 20 Gy (range: 14–20 Gy). The overall response rate was 88.8% (95% CI 83.3–92.7%) while pre- and post-treatment mean VAS was 5.3 (± 7.7) and 2.2 (± 2.2), respectively (p 7) pain (36.0% vs 14.3%; p = 0.028). This pooled analysis showed high efficacy of the SHARON regimen in the relief of several cancer-related symptoms. The markedly and significantly higher complete pain response rate, in patients with mild-moderate pain, suggests early referral to palliative RT for patients with cancer-related pain.

Sarcopenia (SP) is a syndrome characterized by age-associated loss of skeletal muscle mass and function. SP worsens both acute and late radiation-induced toxicity, prognosis, and quality of life. Myosteatosis is a pathological infiltration of muscle tissue by adipose tissue which often precedes SP and has a proven correlation with prognosis in cancer patients. Sarcopenic obesity is considered a “hidden form” of SP (due to large fat mass) and is independently related to higher mortality and worse complications after surgery and systemic treatments with worse prognostic impact compared to SP alone. The evaluation of SP is commonly based on CT images at the level of the middle of the third lumbar vertebra. On this scan, all muscle structures are contoured and then the outlined surface area is calculated. Several studies reported a negative impact of SP on overall survival in patients undergoing RT for tumors of the head and neck, esophagus, rectum, pancreas, cervix, and lung. Furthermore, several appetite-reducing side effects of RT, along with more complex radiation-induced mechanisms, can lead to SP through, but not limited to, reduced nutrition. In particular, in pediatric patients, total body irradiation was associated with the onset of SP and other changes in body composition leading to an increased risk of cardiometabolic morbidity in surviving adults. Finally, some preliminary studies showed the possibility of effectively treating SP and preventing the worsening of SP during RT. Future studies should be able to provide information on how to prevent and manage SP before, during, or after RT, in both adult and pediatric patients.

Palliative radiotherapy (PRT) is known to be effective in relieving cancer related symptoms. However, many studies and clinical practice show several barriers hindering its use and worsening the quality of patient support during PRT. Various solutions were proposed to overcome these barriers: training on PRT for supportive and palliative care specialists and training on palliative care for radiation oncologists, and introduction of pathways and organizational models specifically dedicated to PRT. Evidence on innovative organizational models and mutual training experiences is few and sparse. Therefore, the aim of this literature review is to present a quick summary of the information available on improving the PRT quality through training, new pathways, and innovative organizational models. The majority of studies on the integration of PRT with other palliative and supportive therapies present low levels of evidence being mostly retrospective analyses. However, it should be emphasized that all reports uniformly showed advantages coming from the integration of PRT with supportive therapies. To actively participate in the integration of PRT and palliative care, providing comprehensive support to the needs of patients with advanced cancer, radiation oncologists should not only plan PRT but also: (i) assess and manage symptoms and stress, (ii) rapidly refer patients to specialists in management of more complex symptoms, and (iii) participate in multidisciplinary palliative care teams. To this end, improved education in palliative care both in residency schools and during professional life through continuous medical education is clearly needed. In particular, effective training is needed for radiotherapy residents to enable them to provide patients with comprehensive palliative care. Therefore, formal teaching of adequate duration, interactive teaching methods, attendance in palliative care services, and education in advanced palliative care should be planned in post-graduated schools of radiotherapy.

Background: The safe use of radiotherapy (RT) requires compliance with dose/volume constraints (DVCs) for organs at risk (OaRs). However, the available recommendations are sometimes conflicting and scattered across a number of different documents. Therefore, the aim of this work is to provide, in a single document, practical indications on DVCs for OaRs in external beam RT available in the literature. Material and Methods: A multidisciplinary team collected bibliographic information on the anatomical definition of OaRs, on the imaging methods needed for their definition, and on DVCs in general and in specific settings (curative RT of Hodgkin’s lymphomas, postoperative RT of breast tumors, curative RT of pediatric cancers, stereotactic ablative RT of ventricular arrythmia). The information provided in terms of DVCs was graded based on levels of evidence. Results: Over 650 papers/documents/websites were examined. The search results, together with the levels of evidence, are presented in tabular form. Conclusions: A working tool, based on collected guidelines on DVCs in different settings, is provided to help in daily clinical practice of RT departments. This could be a first step for further optimizations.

Severe pain is frequent in patients with locally advanced pancreatic ductal adenocarcinoma (PDCA). Stereotactic body radiotherapy (SBRT) provides high local control rates in these patients. The aim of this review was to systematically analyze the available evidence on pain relief in patients with PDCA. We updated our previous systematic review through a search on PubMed of papers published from 1 January 2018 to 30 June 2021. Studies with full available text, published in English, and reporting pain relief after SBRT on PDCA were included in this analysis. Statistical analysis was carried out using the MEDCALC statistical software. All tests were two-sided. The I2 statistic was used to quantify statistical heterogeneity (high heterogeneity level: >50%). Nineteen papers were included in this updated literature review. None of them specifically aimed at assessing pain and/or quality of life. The rate of analgesics reduction or suspension ranged between 40.0 and 100.0% (median: 60.3%) in six studies. The pooled rate was 71.5% (95% CI, 61.6–80.0%), with high heterogeneity between studies (Q2 test: p < 0.0001; I2 = 83.8%). The rate of complete response of pain after SBRT ranged between 30.0 and 81.3% (median: 48.4%) in three studies. The pooled rate was 51.9% (95% CI, 39.3–64.3%), with high heterogeneity (Q2 test: p < 0.008; I2 = 79.1%). The rate of partial plus complete pain response ranged between 44.4 and 100% (median: 78.6%) in nine studies. The pooled rate was 78.3% (95% CI, 71.0–84.5%), with high heterogeneity (Q2 test: p < 0.0001; I2 = 79.4%). A linear regression with sensitivity analysis showed significantly improved overall pain response as the EQD2α/β:10 increases (p: 0.005). Eight papers did not report any side effect during and after SBRT. In three studies only transient acute effects were recorded. The results of the included studies showed high heterogeneity. However, SBRT of PDCA resulted reasonably effective in producing pain relief in these patients. Further studies are needed to assess the impact of SBRT in this setting based on Patient-Reported Outcomes.

PurposeRadiation-induced skin toxicity is a common and distressing side effect of breast radiation therapy (RT). We investigated the use of quantitative spectrophotometric markers as input parameters in supervised machine learning models to develop a predictive model for acute radiation toxicity.Methods and materialsOne hundred twenty-nine patients treated for adjuvant whole-breast radiotherapy were evaluated. Two spectrophotometer variables, i.e. the melanin (IM) and erythema (IE) indices, were used to quantitatively assess the skin physical changes. Measurements were performed at 4-time intervals: before RT, at the end of RT and 1 and 6 months after the end of RT. Together with clinical covariates, melanin and erythema indices were correlated with skin toxicity, evaluated using the Radiation Therapy Oncology Group (RTOG) guidelines. Binary group classes were labeled according to a RTOG cut-off score of ≥ 2. The patient’s dataset was randomly split into a training and testing set used for model development/validation and testing (75%/25% split). A 5-times repeated holdout cross-validation was performed. Three supervised machine learning models, including support vector machine (SVM), classification and regression tree analysis (CART) and logistic regression (LR), were employed for modeling and skin toxicity prediction purposes.ResultsThirty-four (26.4%) patients presented with adverse skin effects (RTOG ≥2) at the end of treatment. The two spectrophotometric variables at the beginning of RT (IM,T0 and IE,T0), together with the volumes of breast (PTV2) and boost surgical cavity (PTV1), the body mass index (BMI) and the dose fractionation scheme (FRAC) were found significantly associated with the RTOG score groups (p

Background: In our department, we provided guidelines to the radiation oncologists (ROs) regarding the omission, delay, or shortening of radiotherapy (RT). The purpose was to reduce the patients’ exposure to the hospital environment and to minimize the departmental overcrowding. The aim was to evaluate the ROs’ compliance to these guidelines. Methods: ROs were asked to fill out a data collection form during patients’ first visits in May and June 2020. The collected data included the ROs’ age and gender, patient age and residence, RT purpose, treated tumor, the dose and fractionation that would have been prescribed, and RT changes. The chi-square test and binomial logistic regression were used to analyze the correlation between the treatment prescription and the collected parameters. Results: One hundred and twenty-six out of 205 prescribed treatments were included in this analysis. Treatment was modified in 61.1% of cases. More specifically, the treatment was omitted, delayed, or shortened in 7.9, 15.9, and 37.3% of patients, respectively. The number of delivered fractions was reduced by 27.9%. A statistically significant correlation (p = 0.028) between younger patients’ age and lower treatment modifications rate was recorded. Conclusion: Our analysis showed a reasonably high compliance of ROs to the pandemic-adapted guidelines. The adopted strategy was effective in reducing the number of admissions to our department.

BackgroundSarcopenia (SP) is defined as the quantitative and functional impairment of skeletal muscles. SP is commonly related to older age and is frequent in patients with cancer. To provide an overview of SP in patients treated with radiotherapy (RT) and to evaluate the current evidence, we analyzed the available systematic reviews and meta-analyses.MethodsReviews were identified using PubMed, Scopus, and Cochrane library databases, without date restriction. Only systematic reviews and meta-analyses on the prognostic impact of SP and on any treatments aimed at reducing SP effect, in patients undergoing RT, were included in this review. The analyses not separately reporting the results in patients treated with RT were excluded. The quality assessment was performed using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews).ResultsFrom the 84 papers identified, five reviews met the inclusion criteria with four reports mainly including non-randomized trials. Three reviews on the effect of SP showed a significantly negative impact on overall survival in patients undergoing RT and/or chemoradiation for H&N cancers (HR: 1.63-2.07). Two reviews on interventional studies showed the possibility of 1) improving physical functions through nutritional and physical interventions and 2) avoiding muscle wasting by means of sufficient protein intake. The quality assessment of the included review showed that two and three analyses are classifiable as having low and moderate overall confidence rating, respectively.ConclusionsThe analyzed reviews uniformly confirmed the negative impact of SP in patients with H&N tumors undergoing RT and the possibility of improving muscle mass and function through nutritional and physical interventions. These results justify further research on this topic based on a more uniform SP definition and on a complete evaluation of the potentially confounding parameters.

Abstract Conventionally fractionated chemoradiation (CRT) or chemotherapy (CHT) are considered as standard options in locally advanced pancreatic cancer (LAPC) while stereotactic body radiotherapy (SBRT) is an emerging treatment in this setting. The aim of this study was to compare two cohorts of LAPC patients treated with SBRT ± CHT vs CRT ± CHT in terms of local control (LC), distant metastases‐free survival (DMFS), progression‐free survival (PFS), overall survival (OS), and toxicity. Eighty patients were included. Patients in the two cohorts were matched according to: age ≤/>65 years, tumor diameter (two cut‐offs:

Abstract Background It has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients. Methods A retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and “any site”. The correlation with RT technique was analysed using log-rank test and Cox’s proportional hazard method. Results With a median follow-up of 72 months (range: 9–185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9–152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p: .627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%; p: .033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07–5.47, p: .034). Conclusions The incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results.

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/MethodsThe 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.ResultsFor 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 15 and 23 min for Pers and AP plans, respectively. The average beam-on times were found to be within 3 min for all plans. Despite the increased complexity, all plans passed the 2%/2 mm γ-analysis for dose verification.ConclusionAutomated planning for spine SBRT through the new Pinnacle3 Personalized engine provided an overall increase of plan quality in terms of dose conformity and a major increase in efficiency. In this complex anatomical site, Personalized strongly reduce the tradeoff between optimal accurate dosimetry and planning time.

AimThe 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.MethodsA 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.ResultsTwelve 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.ConclusionNone 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 Registrationwww.crd.york.ac.uk/prospero/, identifier CRD42020206639.

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 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.

BackgroundIn radiation oncology, automation of treatment planning has reported the potential to improve plan quality and increase planning efficiency. We performed a comprehensive dosimetric evaluation of the new Personalized algorithm implemented in Pinnacle3 for full planning automation of VMAT prostate cancer treatments.Material and MethodsThirteen low-risk prostate (without lymph-nodes irradiation) and 13 high-risk prostate (with lymph-nodes irradiation) treatments were retrospectively taken from our clinical database and re-optimized using two different automated engines implemented in the Pinnacle treatment system. These two automated engines, the currently used Autoplanning and the new Personalized are both template-based algorithms that use a wish-list to formulate the planning goals and an iterative approach able to mimic the planning procedure usually adopted by experienced planners. In addition, the new Personalized module integrates a new engine, the Feasibility module, able to generate an “a priori” DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually generated (MP) and automated plans generated with both Autoplanning (AP) and Personalized engines (Pers) were performed using dose-volume histogram metrics and conformity indexes. Three different normal tissue complication probabilities (NTCPs) models were used for rectal toxicity evaluation. The planning efficiency and the accuracy of dose delivery were assessed for all plans.ResultsFor similar targets coverage, Pers plans reported a significant increase of dose conformity and less irradiation of healthy tissue, with significant dose reduction for rectum, bladder, and femurs. On average, Pers plans decreased rectal mean dose by 11.3 and 8.3 Gy for low-risk and high-risk cohorts, respectively. Similarly, the Pers plans decreased the bladder mean doses by 7.3 and 7.6 Gy for low-risk and high-risk cohorts, respectively. The integral dose was reduced by 11–16% with respect to MP plans. Overall planning times were dramatically reduced to about 7 and 15 min for Pers plans. Despite the increased complexity, all plans passed the 3%/2 mm γ-analysis for dose verification.ConclusionsThe Personalized engine provided an overall increase of plan quality, in terms of dose conformity and sparing of normal tissues for prostate cancer patients. The Feasibility “a priori” DVH prediction module provided OARs dose sparing well beyond the clinical objectives. The new Pinnacle Personalized algorithms outperformed the currently used Autoplanning ones as solution for treatment planning automation.

Abstract 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:

BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled analysis was to evaluate if presurgical CA19-9 level can also predict local control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred patients with PaC from eight institutions who underwent surgical resection ± adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull regression model to identify independent predictors of OS on 404 patients with complete information was fitted. RESULTS: Median follow-up was 17 months (range: 2-225 months). Univariate analysis showed a better prognosis in pT1-2, pN0, diameter 353.1: 10.9%, 50.2%, and 23.4%, respectively. At multivariate analysis, CA19-9 >100 and 30 mm (P50.0 Gy showed improved OS (P

BackgroundGlioblastoma Multiforme (GBM) is the most common primary brain cancer and one of the most lethal tumors. Theoretically, modern radiotherapy (RT) techniques allow dose-escalation due to the reduced irradiation of healthy tissues. This study aimed to define the adjuvant maximum tolerated dose (MTD) using volumetric modulated arc RT with simultaneous integrated boost (VMAT-SIB) plus standard dose temozolomide (TMZ) in GBM.MethodsA Phase I clinical trial was performed in operated GBM patients using VMAT-SIB technique with progressively increased total dose. RT was delivered in 25 fractions (5 weeks) to two planning target volumes (PTVs) defined by adding a 5-mm margin to the clinical target volumes (CTVs). The CTV1 was the tumor bed plus the MRI enhancing residual lesion with 10-mm margin. The CTV2 was the CTV1 plus 20-mm margin. Only PTV1 dose was escalated (planned dose levels: 72.5, 75, 77.5, 80, 82.5, 85 Gy), while PTV2 dose remained unchanged (45 Gy/1.8 Gy). Concurrent and sequential TMZ was prescribed according to the EORTC/NCIC protocol. Dose-limiting toxicities (DLTs) were defined as any G ≥ 3 non-hematological acute toxicity or any G ≥ 4 acute hematological toxicities (RTOG scale) or any G ≥ 2 late toxicities (RTOG-EORTC scale).ResultsThirty-seven patients (M/F: 21/16; median age: 59 years; median follow-up: 12 months) were enrolled and treated as follows: 6 patients (72.5 Gy), 10 patients (75 Gy), 10 patients (77.5 Gy), 9 patients (80 Gy), 2 patients (82.5 Gy), and 0 patients (85 Gy). Eleven patients (29.7%) had G1-2 acute neurological toxicity, while 3 patients (8.1%) showed G ≥ 3 acute neurological toxicities at 77.5 Gy, 80 Gy, and 82.5 Gy levels, respectively. Since two DLTs (G3 neurological: 1 patient and G5 hematological toxicity: 1 patient) were observed at 82.5 Gy level, the trial was closed and the 80 Gy dose-level was defined as the MTD. Two asymptomatic histologically proven radionecrosis were recorded.ConclusionsAccording to the results of this Phase I trial, 80 Gy in 25 fractions accelerated hypofractionated RT is the MTD using VMAT-SIB plus standard dose TMZ in resected GBM.

Purpose: The standard primary treatment for soft tissue sarcoma (STS) is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT) plus postoperative external beam radiation therapy (EBRT) in patients with intermediate-high risk STS. Material and methods : BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT) was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS) and local control (LC) in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS), and OS. Results : From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC) primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015), and in lower limb tumors vs. other sites (p = 0.027). An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034). Conclusions : The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC.

Pancreatic cancer remains one of the leading causes of cancer deaths. Despite improvements in imaging, surgical techniques, chemotherapy agents, and radiation techniques, the prognosis for patients with pancreatic adenocarcinoma remains poor. Traditionally, radiotherapy (RT) has been utilized as neoadjuvant, adjuvant, or definitive treatment, and represents an important therapeutic option in pancreatic adenocarcinoma. Intensity-modulated radiation therapy (IMRT), a more recent RT technique, has the potential to deliver an adequate dose to the tumour volume with a minimal dose to the surrounding critical structures such as duodenum, small intestine, liver, kidneys, and spinal cord. This article provides a review about the role of IMRT in the treatment of pancreatic cancer, concerning clinical outcomes such as toxicity, local control, and overall survival.

This analysis evaluates the feasibility and dosimetric results of a simplified intensity-modulated radiotherapy (IMRT) treatment using a cobalt-therapy unit for post-operative breast cancer. Fourteen patients were included. Three plans per patient were produced by a cobalt-60 source: A standard plan with two wedged tangential beams, a standard tangential plan optimized without the use of wedges and a plan based on the forward-planned "field-in-field" IMRT technique (Co-FinF) where the dose on each of the two tangential beams was split into two different segments and the two segments weight was determined with an iterative process. For comparison purposes, a 6-MV photon standard wedged tangential treatment plan was generated. D mean , D 98% , D 2% , V 95% , V 107%, homogeneity, and conformity indices were chosen as parameters for comparison. Co-FinF technique improved the planning target volume dose homogeneity compared to other cobalt-based techniques and reduced maximum doses (D 2% ) and high-dose volume (V 110% ). Moreover, it showed a better lung and heart dose sparing with respect to the standard approach. The higher dose homogeneity may encourage the adoption of accelerated-hypofractionated treatments also with the cobalt sources. This approach can promote the spread of breast conservative treatment in developing countries.