A reduction in tumor volume exceeding 65% predicts a good histological response to neoadjuvant chemotherapy in patients with Ewing sarcoma.

OBJECTIVE: No consensus exists for tumor volume response criteria in patients with Ewing sarcoma. This study aimed to identify an optimal cutoff for predicting a good histological response by analyzing tumor volume changes and tumor necrosis after neoadjuvant chemotherapy. MATERIALS AND METHODS: We performed a retrospective analysis of 184 Ewing sarcoma patients, analyzing tumor volume changes before and after neoadjuvant chemotherapy. Patients were divided into two groups based on histological response: good (tumor necrosis ≥ 95%) and poor (tumor necrosis < 95%) responders. The receiver operating characteristic (ROC) area under the curve (AUC) method was used to determine the optimal thresholds for predicting the histological response. Additionally, the prognostic value of this cutoff for relapse-free survival was assessed. RESULTS: Out of 184 patients, 83 (45%) had tumor necrosis ≥ 95%, while 101 (55%) had tumor necrosis < 95%. ROC analysis identified the optimal cutoff for a good histological response as over 65% tumor volume reduction (AUC = 0.69; p < 0.001). Patients with volume reduction of ≥ 65% had a higher likelihood of a good histological response than those with lesser reductions (p = 0.004; odds ratio = 2.61). Multivariable analysis indicated a correlation between poor histological response and reduced relapse-free survival (hazard ratio = 2.17; p = 0.01), while tumor volume reduction itself did not impact survival. CONCLUSION: We reported that a tumor volume reduction of ≥ 65% was able to predict a good histological response in Ewing sarcoma patients. We recommend preoperative tumor volume assessment to identify patients at greater risk for poor histological response who could benefit from more intensive chemotherapy protocols or additional radiotherapy.

Proton therapy: A therapeutic opportunity for aggressive pediatric meningioma.

Meningiomas are an extremely rare histology among pediatric brain tumors, and there is a shortage of literature on their management. Proton therapy is currently used safely and effectively for many types of both pediatric and adult cancer, and its main advantage is the sparing of healthy tissues from radiation, which could translate in the reduction of late side effects. We review the literature on radiotherapy and proton therapy for pediatric meningiomas and report clinical outcomes for two aggressive pediatric meningiomas we treated with protons. Proton therapy might be a safe and effective therapeutic option for this rare subgroup of tumors.

The role of radiotherapy in adult soft tissues sarcoma of the extremities.

Local management of adult soft tissue sarcoma of the extremities has evolved over the past decades. Until the 1970s, radical surgery (amputations) was the standard therapeutic procedure resulting in significant physical and psychological morbidity for the patients. In the present era, limb sparing surgery combined with radiotherapy represents the current standard of care for high grade and > 5 cm STSs. This approach guarantees high local control rate and function preservation. The aim of this paper is to summarize the current evidence for RT in STSs of the extremities. Outcomes, technical details (techniques, timing, dose, volumes of treatment) and the emerging role of RT in the management of oligometastatic disease will be analysed. Finally, results of the recent clinical trials testing new scenarios in RT of STSs will be described.

Radiotherapy of prostate cancer: impact of treatment characteristics on the incidence of second tumors.

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.

Automated treatment planning as a dose escalation strategy for stereotactic radiation therapy in pancreatic cancer.

PURPOSE: To assess the feasibility of automated stereotactic volumetric modulated arc therapy (SBRT-VMAT) planning using a simultaneous integrated boost (SIB) approach as a dose escalation strategy for SBRT in pancreatic cancer. METHODS: Twelve patients with pancreatic cancer were retrospectively replanned. Dose prescription was 30 Gy to the planning target volume (PTV) and was escalated up to 50 Gy to the boost target volume (BTV) using a SIB technique in 5 fractions. All plans were generated by Pinnacle3 Autoplanning using 6MV dual-arc VMAT technique for flattened (FF) and flattening filter-free beams (FFF). An overlap volume (OLV) between the PRV duodenum and the PTV was defined to correlate with the ability to boost the BTV. Dosimetric metrics for BTV and PTV coverage, maximal doses for serial OARs, integral dose, conformation numbers, and dose contrast indexes were used to analyze the dosimetric results. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Differences between FF and FFF plans were quantified using the Wilcoxon matched-pair signed rank. RESULTS: Full prescription doses to the 95% of PTV and BTV can be delivered to patients with no OLV. BTV mean dose was >90% of the prescribed doses for all patients at all dose levels. Compared to FF plans, FFF plans showed significant reduced integral doses, larger number of MUs, and reduced beam-on-times up to 51% for the highest dose level. Despite plan complexity, pre-treatment verification reported a gamma pass-rate greater than the acceptance threshold of 95% for all FF and FFF plans for 3%-2 mm criteria. CONCLUSIONS: The SIB-SBRT strategy with Autoplanning was dosimetrically feasible. Ablative doses up to 50 Gy in 5 fractions can be delivered to the BTV for almost all patients respecting all the normal tissue constraints. A prospective clinical trial based on SBRT strategy using SIB-VMAT technique with FFF beams seems to be justified.

Definitive Radiotherapy in Invasive Vaginal Carcinoma: A Systematic Review.

AIM: This study systematically reviews the recent literature on the role of definitive radiotherapy (RT) in the management of vaginal cancer (VC) and presents comprehensive data on clinical outcomes and toxicity. METHODS: The authors performed a literature search using PubMed (2007-2016) to identify all prospective and retrospective studies that have been published on RT in invasive VC. RESULTS: Of the 199 identified studies, 13 met the inclusion criteria. All studies had a retrospective design. Overall, 793 patients (median, 45; range, 26-138) were included. A high heterogeneity was found across studies in terms of RT techniques, assessment criteria, and reported outcomes. The majority of the patients were treated with a combination of external beam RT and brachytherapy (74.2%). Acute and late grade ≥3 toxicity rates ranged from 0.0% to 24.4% (median, 8.7%) and from 0.0% to 22.5% (median, 12.8%), respectively. The 5-year local control rates ranged between 39% and 79%. The 5-year overall survival ranged between 34% and 71.0% (median, 63.5%). Early stage of the disease (International Federation of Gynecology and Obstetrics stages I-II vs. III-IV), small tumor size (<4 cm), previous hysterectomy, high pretreatment/treatment hemoglobin levels (≥12/12.5 mg/dL), and patients' age <70 or <64 years were correlated with better clinical outcomes. CONCLUSION: Only retrospective studies, in a limited number, have been published on RT in VC in the past decade, with significant heterogeneity in terms of treatment characteristic and evaluation criteria. Clinical results were strongly influenced by tumor stage. Prospective randomized studies are needed to improve patients' outcomes, especially in advanced-stage disease. IMPLICATIONS FOR PRACTICE: This study systematically reviews the recent literature on the role of definitive radiotherapy in the management of vaginal cancer and presents comprehensive data on clinical outcome and toxicity. The prognosis of patients is dismal, with a 5-year overall survival of approximately 50%. Early stage of the disease, small tumor size, previous hysterectomy, high pretreatment/treatment hemoglobin levels, and patients' age were correlated with a better clinical outcome. A brachytherapy boost should be delivered, especially in patients with higher-stage disease. The addition of concurrent weekly cisplatin should be considered in most patients, and transfusion should be used to maintain high hemoglobin levels.

Prognostic Impact of Pretreatment Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography SUVmax in Patients With Locally Advanced Cervical Cancer.

OBJECTIVE: The aim of this study was to investigate the impact of SUVmax fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) measured in the primary tumor, pelvic and para-aortic node with disease-free survival (DFS) and overall survival (OS) in patients with locally advanced cervical cancer. METHODS AND MATERIALS: A total of 92 patients with histological diagnosis of locally advanced cervical cancer are treated with radiochemotherapy plus brachytherapy boost from January 2008 to April 2014 in our Institution. A pretreatment FDG-PET/CT for staging and radiotherapy planning was performed, and the value of SUVmax measured in primary tumor and positive nodes was related to DFS and OS. RESULTS: Univariate analysis showed that DFS is related to FDG-PET/CT positive para-aortic nodes (P = 0.01), International Federation of Gynecology and Obstetrics (FIGO) stage of disease (P = 0.01), and primary tumor SUVmax (P = 0.02), and OS is related to positive para-aortic nodes (P = 0.01) and primary tumor SUVmax (P = 0.02).In multivariate analysis, DFS is modified by FDG-PET/CT positive para-aortic lymph nodes, stage and high T SUVmax (P = 0.02; P = 0.003; P = 0.04), but the only worse prognostic factor of OS is the high SUVmax in the primary tumor (P = 0.01). CONCLUSIONS: We found that T SUVmax, stage, and para-aortic lymph node status assessed by FDG-PET were independent prognostic factors of DFS, whereas only T SUVmax correlated with OS.

Partially ablative radiotherapy (PAR) for large mass tumors using simultaneous integrated boost: A dose-escalation feasibility study.

PURPOSE: This study aimed to assess the feasibility to plan and deliver highly heterogeneous doses to symptomatic large tumors using volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) during a short course palliative accelerated radiotherapy. METHODS: A patient with a large symptomatic chordoma infiltrating the right gluteal region was selected. A modified SIB treatment was implemented to irradiate the central volume of the tumor (boost target volume, BTV) up to 10 Gy/fraction in a dose escalation trial while maintaining the remaining tumor volume (planning target volume, PTV) and the surrounding healthy tissues within 5 Gy/fraction in twice daily fractions for two consecutive days. Four SIB plans were generated in the dual-arc modality; a basal dose of 20 Gy was prescribed to the PTV, while the BTV was boosted up to 40 Gy. For comparison purposes, plans obtained with a sequential boost (SEQ plans) were also generated. All plans were optimized to deliver at least 95% of the prescription dose to the targets. Dose contrast index (DCI), conformity index (CI), integral dose (ID), and the irradiated body volumes at 5, 10, and 20 Gy were evaluated. RESULTS: At equal targets coverage, SIB plans provided major improvement in DCI, CI, and ID with respect to SEQ plans. When BTV dose escalated up to 200% of PTV prescription, DCI resulted in 66% for SIB plans and 37% for SEQ plans; the ID increase was only 11% for SIB plans (vs 27% for SEQ plans) and the increase in healthy tissues receiving more than 5, 10, and 20 Gy was less than 2%. Pretreatment dose verification reported a γ-value passing rate greater than 95% with 3%(global)-2 mm. CONCLUSION: A modified SIB technique is dosimetrically feasible for large tumors, where doses higher than the tolerance dose of healthy tissues are necessary to increase the therapeutic gain.

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

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

Palliative electro-chemotherapy in elderly patients with vulvar cancer: A phase II trial.

OBJECTIVE: The primary endpoint of this trial was to assess clinical response (cCR) of squamocellular vulvar cancer (V-SCC) in elderly patients treated with electro-chemotherapy (ECT). Secondary endpoints were symptoms relief and local tumor control. METHODS: A phase II study was designed and elderly patients with V-SCC unfit for other treatments were treated. Response Evaluation Criteria in Solid Tumors (RECIST criteria) were applied to evaluate tumor response. Quality of life (QoL) was evaluated by visual analogue score (VAS) for pain and four items of vulvar cancer subscale (VCS), of functional assessment of vulvar cancer therapy (FACT-V) [16], before, one month after the procedure and during follow-up. RESULTS: Median age was 85 years (range 66-96 years). One month after treatment complete response was observed in 13 patients (52%), partial response in 7 (28%), stable disease in 3 (12%), and progressive disease in 2 (8%). Local tumor control at 1 and 6 months was 91% and 53%, respectively. Symptom free survival at 1 and 6 months was 78% and 40%, respectively, with significant reduction of pain (P < 0.01). One-year overall survival was 34%. CONCLUSIONS: Our study showed that ECT produces high response rate with significant reduction of pain and improvement of local symptoms.

Post-relapse survival in patients with Ewing sarcoma.

BACKGROUND: Post-relapse survival (PRS) was evaluated in patients with Ewing sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation treatment in high-risk patients. PROCEDURE: EWS patients enrolled in ISG/SSG III and IV trials who relapsed after complete remission were included in the analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen, and patients who responded but had not received HDT underwent consolidation therapy with HDT. RESULTS: Data from 107 EWS patients were included in the analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients had multiple sites of recurrence. Patients who had previously been treated with HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a second complete remission (CR2). CR2 status was achieved by 42 (39%) patients. Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to 64%). Without CR2, median time to death was six months (range 1-45 months). According to the multivariate analysis, patients younger than 15 years, recurrence to the lung only, and RFI longer than 24 months significantly influenced the probability of PRS. CONCLUSIONS: Age, pattern of recurrence, RFI, and response to second-line chemotherapy influence post-relapse survival in patients with recurrent Ewing sarcoma. No survival advantage was observed from chemotherapy consolidation with HDT.

Augmented reality in brachytherapy: A narrative review.

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.

Personalizing Prophylactic Radiotherapy for Hip Heterotopic Ossification: An AMSTAR-2 Compliant Review of Meta-analyses.

BACKGROUND/AIM: Heterotopic ossification (HO) is a common complication following total hip arthroplasty. Various prophylactic treatments have been proposed, including radiotherapy (RT). This review summarizes the evidence from meta-analyses on the efficacy of RT in preventing hip HO. MATERIALS AND METHODS: A literature search was conducted on PubMed. The quality of the meta-analyses was assessed using the AMSTAR-2 tool. RESULTS: Seven meta-analyses were included. One meta-analysis reported a significant reduction in HO occurrence after RT compared to the control group. Comparing RT and non-steroidal anti-inflammatory drugs, one and two meta-analyses showed significantly greater efficacy of RT in preventing severe HO and better outcomes in patients receiving drugs, respectively. Regarding RT settings, the postoperative and preoperative RT were each supported by one meta-analysis. Furthermore, two meta-analyses showed an advantage of multi-fractionated RT over single fraction RT. The overall confidence rate of the meta-analyses was moderate, low, and critically low in one, three, and three meta-analyses, respectively. CONCLUSION: RT is a confirmed prophylactic intervention for HO. However, the precise optimization of timing, dosage, and fractionation requires elucidation. Future research should focus on the development of predictive models through large-scale data collection and advanced analytics to refine individualized treatment strategies and assess RT comparative effectiveness with drugs.

Sarcopenic Obesity in Cervical Carcinoma: A Strong and Independent Prognostic Factor beyond the Conventional Predictors (ESTHER Study-AFRAID Project).

Locally advanced cervical cancer represents a significant treatment challenge. Body composition parameters such as body mass index, sarcopenia, and sarcopenic obesity, defined by sarcopenia and BMI ≥ 30 kg/m2, have been identified as potential prognostic factors, yet their overall impact remains underexplored. This study assessed the relationship between these anthropometric parameters alongside clinical prognostic factors on the prognosis of 173 cervical cancer patients. Survival outcomes in terms of local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were analyzed using Kaplan regression methods-Meier and Cox. Older age, lower hemoglobin levels, higher FIGO (International Federation of Gynecology and Obstetrics) stages, and lower total radiation doses were significantly associated with worse outcomes. Univariate analysis showed a significant correlation between BMI and the outcomes examined, revealing that normal-weight patients show higher survival rates, which was not confirmed by the multivariate analysis. Sarcopenia was not correlated with any of the outcomes considered, while sarcopenic obesity was identified as an independent negative predictor of DFS (HR: 5.289, 95% CI: 1.298-21.546, p = 0.020) and OS (HR: 2.645, 95% CI: 1.275-5.488, p = 0.009). This study highlights the potential of sarcopenic obesity as an independent predictor of clinical outcomes. These results support their inclusion in prognostic assessments and treatment planning for patients with advanced cervical cancer.

Further Clarification of Pain Management Complexity in Radiotherapy: Insights from Modern Statistical Approaches.

BACKGROUND: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. METHODS: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score < 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. RESULTS: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI < 0) and non-cancer pain (73.1% with PMI < 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. CONCLUSIONS: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care.

The role of training simulators in interventional radiation therapy (brachytherapy) training: A narrative review.

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.

Stereotactic Arrhythmia Radioablation (STAR): A Multidisciplinary Narrative Minireview of Preclinical Studies.

The aim of this narrative review of the literature was to collect and analyze the results of the published preclinical studies on stereotactic arrhythmia radioablation (STAR) in the treatment of refractory cardiac arrhythmias. A literature search was conducted on PubMed using the following terms: ("stereotactic" OR "SBRT" OR "SABR" OR "radioablation" OR "radiosurgery") AND ("arrhythmia" OR "tachycardia"). Preclinical and pathological reports published in English without time limit, comprising studies of STAR in animal models and histological analyzes of explanted animal and human hearts were included. The analyzed studies confirm that doses lower than 25 Gy seem to produce sub-optimal therapeutic results whereas doses >35 Gy are less safe in terms of radiation-induced toxicity. However, long-term results (>1 year) are still missing and reporting outcomes based on low dose irradiation (≤15 Gy). Finally, STAR proved to be an effective therapy in the analyzed studies despite the irradiation of rather different cardiac targets. Therefore, additional studies are needed to: 1) compare the outcomes of STAR at doses of 25 Gy versus 30 Gy; 2) evaluate the long-term results (>1 year) in animal models irradiated at doses similar to those used in the clinic; 3) define the optimal target.

Combination of Electrochemotherapy with Radiotherapy: A Comprehensive, Systematic, PRISMA-Compliant Review of Efficacy and Potential Radiosensitizing Effects in Tumor Control.

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.

Unraveling the safety of adjuvant radiotherapy in prostate cancer: impact of older age and hypofractionated regimens on acute and late toxicity - a multicenter comprehensive analysis.

Background: The 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 methods: This 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. Results: A total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/ß=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). Conclusions: The 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.

Memantine in the Prevention of Radiation-Induced Brain Damage: A Narrative Review.

Preserving cognitive functions is a priority for most patients with brain metastases. Knowing the mechanisms of hyperglutamatergic neurotoxicity and the role of some hippocampal areas in cognitive decline (CD) led to testing both the antiglutamatergic pharmacological prophylaxis and hippocampal-sparing whole-brain radiotherapy (WBRT) techniques. These studies showed a relative reduction in CD four to six months after WBRT. However, the failure to achieve statistical significance in one study that tested memantine alone (RTOG 0614) led to widespread skepticism about this drug in the WBRT setting. Moreover, interest grew in the reasons for the strong patient dropout rates in the first few months after WBRT and for early CD onset. In fact, the latter can only partially be explained by subclinical tumor progression. An emerging interpretation of the (not only) cognitive impairment during and immediately after WBRT is the dysfunction of the limbic and hypothalamic system with its immune and hormonal consequences. This new understanding of WBRT-induced toxicity may represent the basis for further innovative trials. These studies should aim to: (i) evaluate in greater detail the cognitive effects and, more generally, the quality of life impairment during and immediately after WBRT; (ii) study the mechanisms producing these early effects; (iii) test in clinical studies, the modern and advanced WBRT techniques based on both hippocampal-sparing and hypothalamic-pituitary-sparing, currently evaluated only in planning studies; (iv) test new timings of antiglutamatergic drugs administration aimed at preventing not only late toxicity but also acute effects.