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Despite the recent advanced developments in radiation therapy planning, treatment planning for head-neck and pelvic cancers remains challenging due to large concave target volumes, multiple dose prescriptions and numerous organs at risk close to targets. Inter-institutional studies highlighted that plan quality strongly depends on planner experience and skills. Automated optimization of planning procedure may improve plan quality and best practice. We performed a comprehensive dosimetric and clinical evaluation of the Pinnacle 3 AutoPlanning engine, comparing automatically generated plans (AP) with the historically clinically accepted manually-generated ones (MP). Thirty-six patients (12 for each of the following anatomical sites: head-neck, high-risk prostate and endometrial cancer) were re-planned with the AutoPlanning engine. Planning and optimization workflow was developed to automatically generate “dual-arc” VMAT plans with simultaneously integrated boost. Various dose and dose-volume parameters were used to build three metrics able to supply a global Plan Quality Index evaluation in terms of dose conformity indexes, targets coverage and sparing of critical organs. All plans were scored in a blinded clinical evaluation by two senior radiation oncologists. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Autoplanning was able to produce high-quality clinically acceptable plans in all cases. The main benefit of Autoplanning strategy was the improvement of overall treatment quality due to significant increased dose conformity and reduction of integral dose by 6–10%, keeping similar targets coverage. Overall planning time was reduced to 60–80 minutes, about a third of time needed for manual planning. In 94% of clinical evaluations, the AP plans scored equal or better to MP plans. Despite the increased fluence modulation, dose measurements reported an optimal agreement with dose calculations with a γ-pass-rate greater than 95% for 3%(global)-2 mm criteria. Autoplanning engine is an effective device enabling the generation of VMAT high quality treatment plans according to institutional specific planning protocols.

Skin metastases occur in 5–30% of breast cancer (BC) patients. Standard treatments include systemic therapies (chemotherapy, endocrine therapy, and immunotherapy) and local treatments (surgery and radiotherapy). Electrochemotherapy (ECT) could be another option in this setting based on preclinical and clinical studies. Aim of this review was to analyze the available evidence on ECT in skin metastases from BC. Studies reporting on ECT in skin metastases from BC were included in this review. Studies not reporting toxicity or tumor response or not reporting results separately from other primary cancers were excluded. The search was based on Medline, Scopus, and The Cochrane Library databases. Eleven studies including 464 patients were analyzed. ECT was performed using intravenous/intratumoral bleomycin (10 studies) or intratumoral cisplatin (one study). Complete and overall pooled response rates were 46.2% (95%CI 33.2–59.4 and 74.6% (95%CI 60.6–86.4) in studies reporting results on a per patient basis and 61.9% (95%CI 53.8–69.6) and 86.9% (95%CI 80.0–92.6) in studies reporting results on a per lesion basis, respectively. Worse response rates in larger lesions were observed in three studies. The incidence of toxicity was heterogeneous but adverse events were mild and manageable in all studies. One- and 3-year local progression-free survival was 86.2% and 81.0% in two studies, respectively. ECT is tolerable and effective in terms of response in BC skin metastases especially in less advanced lesions. Further studies are justified to compare ECT with other treatments in this setting.

The management of large bulky tumors is very challenging. The current treatment options for effective palliation of symptoms are limited. These tumors often present a large burden at the time of diagnosis, growing along critical bony and neural structures and preventing surgical resection in most of the cases. These tumors are also known to be relatively resistant to chemotherapy, with very low response rates. In addition, conventional photon-based radiotherapy has a limited effect due to their radioresistance, the use of large treatment fields, and the impossibility of delivering high doses because of the higher risk of normal tissue toxicity. Therefore, more effective radiation treatments for palliation are needed to achieve greater local control rates. A recent approach called partial ablative radiotherapy (PART) has been shown to be potentially able to improve the effectiveness of radiotherapy. This technique is based on the ability of recent advanced delivery techniques to deliver a high “ablative” dose to the central part of the tumor, maintaining a very low and safe dose profile at the periphery to spare the surrounding organs at risk. Although this technique has been evaluated only in small studies and case reports, it showed notable treatment responses and safety profiles. The present narrative review describes the rationale for PART, the current and forthcoming state of evidence, the existing studies, and the future directions for the development of this approach, including the associated challenges.

Background: This study aimed to develop a predictive model for acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated with salvage radiotherapy (SRT) post-prostatectomy, using machine learning techniques to identify key prognostic factors. Methods: A multicenter retrospective study analyzed 454 patients treated with SRT from three Italian radiotherapy centers. Acute toxicity was assessed using Radiation Therapy Oncology Group criteria. Predictors of grade ≥ 2 toxicity were identified through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Classification and Regression Tree (CART) modeling. The analyzed variables included surgical technique, clinical target volume (CTV) to planning target volume (PTV) margins, extent of lymphadenectomy, radiotherapy technique, and androgen-deprivation therapy (ADT). Results: No patients experienced grade ≥ 4 toxicity, and grade 3 toxicity was below 1% for both GI and GU events. The primary determinant of acute toxicity was the surgical technique. Open prostatectomy was associated with significantly higher grade ≥ 2 GI (41.8%) and GU (35.9%) toxicity compared to laparoscopic/robotic approaches (18.9% and 12.2%, respectively). A CTV-to-PTV margin ≥ 10 mm further increased toxicity, particularly when combined with extensive lymphadenectomy. SRT technique and ADT were additional predictors in some subgroups. Conclusions: SRT demonstrated excellent tolerability. Surgical technique, CTV-to-PTV margin, and treatment parameters were key predictors of toxicity. These findings emphasize the need for personalized treatment strategies integrating surgical and radiotherapy factors to minimize toxicity and optimize outcomes in prostate cancer patients.

Palliative radiotherapy (PRT) is central to symptom control in advanced cancer, yet referrals are often late, and patients and clinicians frequently hold misconceptions about intent, benefits, and logistics. Patient education may address these gaps, but the PRT-specific evidence base has not been consolidated. We conducted a narrative review following SANRA guidance. We searched PubMed, Scopus, and the Cochrane Library for English-language studies from 1 January 2000 to 18 July 2025. Eligible articles evaluated structured patient-education interventions or characterized education or communication content, information needs, or decision processes among adults referred to or receiving PRT. Two reviewers independently screened and extracted data. Owing to heterogeneity of designs and endpoints, we performed a narrative synthesis without meta-analysis. Six studies met criteria: two randomized controlled trials, two prospective pre–post studies, one qualitative interview study, and one observational communication study, conducted in the Netherlands, the United States, Canada, and Hong Kong. Education at referral or consultation improved knowledge, reduced decisional uncertainty, and increased readiness to proceed with PRT. Education integrated with treatment improved symptom outcomes, including higher rates of pain control at 12 weeks and faster time to pain control when a nurse-led pain-education program accompanied PRT for painful bone metastases, and improvements in dyspnea, fatigue, anxiety, and function in advanced lung cancer. Observational and qualitative work showed low patient question-asking and persistent curative expectations; overall quality of life generally did not change. Although the evidence is limited and heterogeneous, targeted, standardized education appears to improve decision quality and selected symptoms in PRT pathways. Pragmatic multi-site trials and implementation studies are needed to define content, timing, personnel, and delivery models that are scalable in routine care.

In a recent multicenter analysis of 454 patients undergoing post-prostatectomy salvage radiotherapy, the open surgical approach, as opposed to minimally invasive surgery, emerged, unexpectedly, as the strongest predictor of acute gastrointestinal and genitourinary toxicity. Patients treated with laparoscopic or robotic prostatectomy experienced significantly lower rates of ≥grade 2 toxicity compared to those who had undergone open retropubic surgery, irrespective of total dose, treatment margins, or radiation delivery platform. This finding, which to our knowledge has not been previously reported, raises the hypothesis that surgical technique leaves a lasting biological imprint on irradiated tissues. Drawing on current knowledge in radiobiology, cytokine signaling, wound healing, and pelvic dosimetry, we explore potential mechanisms by which open surgery may create a more hypoxic, inflamed, and fibrotic microenvironment, thereby amplifying radiation damage. We further discuss how target volume margins may biologically interact with this tissue state to increase normal tissue exposure. This Perspective aims to provide a conceptual framework for understanding this unexpected association, highlighting its clinical relevance for individualizing margins, counselling high-risk patients, and designing future studies at the interface of surgery and radiation oncology. This paper does not introduce additional patients or statistical models; instead, it offers an in-depth clinical and mechanistic interpretation of previously published ICAROS findings.

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

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.

Stereotactic body radiotherapy (SBRT) has been shown to achieve high local control rates in limited metastatic burden of disease. Few papers reported on the efficacy of SBRT in nodal oligometastases. The primary aim of the present paper was to analyze the treatment outcome in this setting. Data from DESTROY-1 and SRS-DESTROY-2 phase I clinical trials were reviewed and analyzed. These trials were based on a 5 fractions and a single fraction regimens, respectively. End-points of this analysis were toxicity rates, overall response rate (ORR), and local control (LC). Patients treated between December 2003 and January 2018, with any metastatic site, and primary tumor type and histology were included. One hundred-eighty-one patients (M/F: 93/88; median age: 67, range 37–88) treated with SBRT on 253 nodal lesions were analyzed. Initially, the used technique was 3D-CRT (20.9%), while subsequently treatments were delivered by VMAT (79.1%). The total dose to the PTV ranged between 12 Gy/single fraction to 50 Gy/5 fractions. With a median follow-up of 21 months (2–124), no grade 3 acute or late toxicity was recorded. ORR based on functional imaging was 92.5% with a complete response rate of 76%. Two- and three-year actuarial LC were 81.6% and 76.0%, respectively. Our large pooled analysis confirms the efficacy and safety of SBRT/SRS in patients with nodal metastases and identifies clinical and treatment variables able to predict complete response and local control rate.

This narrative review explores the potential role of electrochemotherapy (ECT) in treating anorectal tumors, focusing on its effectiveness, feasibility, and associated toxicities. ECT, which combines chemotherapy with the application of an electric field to enhance drug uptake by tumor cells, has shown promise as a local treatment, particularly in cases where conventional therapies such as radiotherapy have been exhausted or are unsuitable. The review, conducted according to SANRA guidelines, included 18 studies, on ECT in anorectal tumors, ranging from preclinical trials in dogs to case reports and clinical studies in humans. The findings indicate that ECT can achieve high tumor overall response rates (70-100%) with minimal side effects, offering benefits such as tumor reduction and preserved organ function. These results highlight the potential of ECT to provide not only tumor reduction but also the preservation of vital organ function with a relatively low toxicity profile. However, further comparative research is necessary to substantiate its role as a standard therapeutic option. Moreover, the evidence is limited by significant heterogeneity across studies, small sample sizes, and a lack of comparative research with other local treatments like radiotherapy and cryosurgery. Consequently, while ECT appears to be a promising option, particularly for palliative care or in a neoadjuvant setting, it cannot yet be recommended as a standard treatment. Future research should focus on larger, more robust studies with standardized outcomes and explore the potential synergy between ECT and other therapies to establish its place in the treatment of anorectal tumors.