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.

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.

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.

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.

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.

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.

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.

Short course palliative radiotherapy in advanced solid tumors: a pooled analysis (the SHARON project).

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 < 0.001). The overall response rate of pain, dyspnea, bleeding, dysphagia, and other symptoms was 86.2%, 90.9%, 100%, 87.5%, and 100%, respectively. Comparing the symptomatic effect based on the analyzed parameters no significant differences were recorded. However, patients with locally advanced disease showed a higher rate of symptomatic responses than metastatic ones (97.3% vs 83.0%; p = 0.021). Finally, the complete pain response rate was more than double in patients with mild to moderate (VAS: 4-7) compared to those with severe (VAS > 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.

Dose-Volume Constraints fOr oRganS At risk In Radiotherapy (CORSAIR): An "All-in-One" Multicenter-Multidisciplinary Practical Summary.

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.

Stereotactic radiotherapy of nodal oligometastases from prostate cancer: a prisma-compliant systematic review.

Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastases-directed therapies can delay the initiation or switch of systemic treatments and allow local control (LC) and prolonged progression-free survival (PFS), particularly in patients with lymph nodes (LN) oligometastases. We performed a systematic review on stereotactic body radiotherapy (SBRT) in this setting. Papers reporting LC and/or PFS were selected. Data on ADT-free survival, overall survival, and toxicity were also collected from the selected studies. Fifteen studies were eligible (414 patients), 14 of them were retrospective analyses. A high heterogeneity was observed in terms of patient selection and treatment. In one study SBRT was delivered as a single 20 Gy fraction, while in the others the median total dose ranged between 24 and 40 Gy delivered in 3-6 fractions. LC and PFS were reported in 15 and 12 papers, respectively. LC was reported as a crude percentage in 13 studies, with 100% rate in seven and 63.2-98.0% in six reports. Five studies reported actuarial LC (2-year LC: 70.0-100%). PFS was reported as a crude rate in 11 studies (range 27.3-68.8%). Actuarial 2-year PFS was reported in four studies (range 30.0-50.0%). SBRT tolerability was excellent, with only two patients with grade 3 acute toxicity and two patients with grade 3 late toxicity. SBRT for LN oligorecurrences from PCa in safe and provides optimal LC. However, the long-term effect on PFS and OS is still unclear as well as which patients are the best candidate for this approach.

Electrochemotherapy of skin metastases from malignant melanoma: a PRISMA-compliant systematic review.

The main treatment of MM metastases are systemic therapies, surgery, limb perfusion, and intralesional talimogene laherparepvec. Electrochemotherapy (ECT) is potentially useful also due to the high response rates recorded in cancers of any histology. No randomized studies comparing ECT with other local therapies have been published on this topic. We analyzed the available evidence on efficacy and toxicity of ECT in this setting. PubMed, Scopus, and Cochrane databases were screened for paper about ECT on MM skin metastases. Data about tumor response, mainly in terms of overall response rate (ORR), toxicity (both for ECT alone and in combination with systemic treatments), local control (LC), and overall survival (OS) were collected. The methodological quality was assessed using a 20-item validated quality appraisal tool for case series. Overall, 18 studies were included in our analysis. In studies reporting "per patient" tumor response the pooled complete response (CR) was 35.7% (95%CI 26.0-46.0%), and the pooled ORR was 80.6% (95%CI 68.7-90.1%). Regarding "per lesion" response, the pooled CR was 53.5% (95%CI 42.1-64.7%) and the pooled ORR was 77.0% (95%CI 56.0-92.6%). One-year LC rate was 80%, and 1-year OS was 67-86.2%. Pain (24.2-92.0%) and erythema (16.6-42.0%) were the most frequent toxicities. Two studies reported 29.2% and 41.6% incidence of necrosis. ECT is effective in terms of tumor response and tolerated in patients with skin metastases from MM, albeit with a wide variability of reported results. Therefore, prospective trials in this setting are warranted.

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.

Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study.

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites. Proton therapy (PT) has similar efficacy compared to traditional photon-based radiotherapy but might achieve lower toxicity rates. We report on our multi-centric experience with 43 children with medulloblastoma (median age at diagnosis 8.7 years, IQR 6.6, M/F 23/20; 26 high-risk, 14 standard-risk, 3 ex-infant), who received active scanning PT between 2015 and 2021, with a focus on PT-related acute-subacute toxicity, as well as some preliminary data on late toxicity. Most acute toxicities were mild and manageable with supportive therapy. Hematological toxicity was limited, even among HR patients who underwent hematopoietic stem-cell transplantation before PT. Preliminary data on late sequelae were also encouraging, although a longer follow-up is needed.

Pain Relief after Stereotactic Radiotherapy of Pancreatic Adenocarcinoma: An Updated Systematic Review.

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/ß: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.

A SHort course Accelerated RadiatiON therapy (SHARON) dose-escalation trial in older adults head and neck non-melanoma skin cancer.

OBJECTIVES: To assess feasibility and safety of a SHort-course Accelerated RadiatiON therapy (SHARON) regimen, in the treatment of non-melanoma skin cancers (NMSC) in older patients. METHODS: Old patients (age ≥ 80 years) with histological confirmed non-melanoma skin cancers were enrolled. The primary endpoint was to determine the maximum tolerated dose (MTD). Radiotherapy regimen was based on the delivery of four radiotherapy fractions (5 Gy per fraction) with a twice daily fractionation in two consecutive days. Three different level of dose were administered: 20 Gy (one cycle), 40 Gy (two cycles) and 60 Gy (three cycles). RESULTS: Thirty patients (median age: 91 years; range: 80-96) were included in this analysis. Among fourteen patients who completed the one cycle, only one (7%) experimented acute G4 skin toxicity. Twelve patients reported an improvement or resolution of baseline symptoms (overall palliative response rate: 85.8%). Nine and seven patients underwent to two and three RT cycles, respectively: of these, no G3 toxicities were recorded. The overall response rate was 100% when three cycles were delivered. The overall six-month symptom-free survival was 78.7% and 77.8% in patients treated with one course and more courses, respectively. CONCLUSIONS: Short-course accelerated radiotherapy in older patients with non-melanoma skin cancers is well tolerated. High doses seem to be more effective in terms of response rate. ADVANCES IN KNOWLEDGE: This approach could represent an option for older adults with NMSC, being both palliative (one course) or potentially curative (more courses) in the aim, accordingly to the patient's condition.

CARE-compliant stereotactic radiotherapy of urothelial nodal metastases: A case report.

The aim of the present study was to report the case of a 58-year-old male patient with ureteral carcinoma who underwent ureteroileostomy treatment. At 2 years following surgery, six lymph node metastases (LNMs) were detected in the patient's para-aortic and pelvic regions using 18F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT. All LNMs were treated using stereotactic body radiotherapy (SBRT; 35-40 Gy/5 fractions). At 3 months after radiotherapy, 18F-FDG-PET/CT examination revealed a complete radiological and metabolic response of all targeted treatment sites in the patient. In the 2 years following radiotherapy, another three same-dose SBRT treatments were performed on single or multiple LNMs, which were all detected in the abdomen and pelvis of the patient. Overall, a total of 11 LNMs were targeted in the patient and all exhibited complete radiological and metabolic response following treatment. The only treatment side effect reported by the patient was a slight and temporary loss of appetite. In patients with lymph node oligometastases there are two options for radiotherapy: i) Irradiation focusing on LNMs alone; and ii) prophylactic irradiation of the entire lymph node area combined with a boost on macroscopic lesions. In the patient discussed in the present study, the choice of irradiation focusing on LNMs alone made it possible to postpone systemic therapies and instead use an optimally tolerated treatment. The treatment outcome in this patient indicated that there was no radioresistance of urothelial LNMs.

Prophylactic Radiotherapy of Hip Heterotopic Ossification: A Narrative Mini Review.

Evidence on prophylactic radiotherapy (RT) in hip heterotopic ossification (HO) is sparse and conflicting. The aim of this literature review was to collect and summarize the available data on RT efficacy in preventing hip HO. The results of this review show that RT is effective in the prevention of hip HO, albeit with large variability across series. Effective prophylactic RT requires optimal treatment fields and time intervals with surgery. On the contrary, there is no clear evidence on the optimal timing (post-operative versus pre-operative RT). Comparisons between prophylactic RT and use of non-steroidal anti-inflammatory drugs showed conflicting results, although most were in favor of RT. In conclusion, RT is an established prophylactic treatment for hip HO. However, optimal dose, technique and timing remain unclear, as does the usefulness of combining RT with drugs.

Improving total body irradiation with a dedicated couch and 3D-printed patient-specific lung blocks: A feasibility study.

Introduction: Total body irradiation (TBI) is an important component of the conditioning regimen in patients undergoing hematopoietic stem cell transplants. TBI is used in very few patients and therefore it is generally delivered with standard linear accelerators (LINACs) and not with dedicated devices. Severe pulmonary toxicity is the most common adverse effect after TBI, and patient-specific lead blocks are used to reduce mean lung dose. In this context, online treatment setup is crucial to achieve precise positioning of the lung blocks. Therefore, in this study we aim to report our experience at generating 3D-printed patient-specific lung blocks and coupling a dedicated couch (with an integrated onboard image device) with a modern LINAC for TBI treatment. Material and methods: TBI was planned and delivered (2Gy/fraction given twice a day, over 3 days) to 15 patients. Online images, to be compared with planned digitally reconstructed radiographies, were acquired with the couch-dedicated Electronic Portal Imaging Device (EPID) panel and imported in the iView software using a homemade Graphical User Interface (GUI). In vivo dosimetry, using Metal-Oxide Field-Effect Transistors (MOSFETs), was used to assess the setup reproducibility in both supine and prone positions. Results: 3D printing of lung blocks was feasible for all planned patients using a stereolithography 3D printer with a build volume of 14.5×14.5×17.5 cm3. The number of required pre-TBI EPID-images generally decreases after the first fraction. In patient-specific quality assurance, the difference between measured and calculated dose was generally<2%. The MOSFET measurements reproducibility along each treatment and patient was 2.7%, in average. Conclusion: The TBI technique was successfully implemented, demonstrating that our approach is feasible, flexible, and cost-effective. The use of 3D-printed patient-specific lung blocks have the potential to personalize TBI treatment and to refine the shape of the blocks before delivery, making them extremely versatile.

Clinical Studies on Ultrafractionated Chemoradiation: A Systematic Review.

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