Purpose:Abscopal effects (AbE) during combined radiotherapy (RT) and immune checkpoint inhibition (ICI) represent a potential mechanism for systemic tumor control, yet sex-specific differences in these responses remain largely unexplored. We investigated sex-associated signals in outcomes of combined RT-ICI in a multicenter cohort. We analyzed the incidence of AbE and survival outcomes with respect to clinical and biomedical markers. Methods:In this observational multicenter study, patients with metastatic solid tumors receiving RT-ICI and showing at least one non-irradiated lesion (NIL), assessed using iRECIST criteria, were analyzed. Abscopal response (AR) was defined as ≥30% reduction in NIL size, abscopal progression (AP) as ≥20% increase, and abscopal control (AC) as changes within this range. Results:Among 3,773 screened patients, 142 met the inclusion criteria (62% male, median age 62 years; 38% female, median age 58 years). AR and AC occurred more frequently in females (24% vs. 14%, 35% vs. 31%). While OS showed no significant difference (p=0.81), Cox regression analyses revealed significant associations of a longer ICI-to-RT-interval (males: HR = 0.903 [0.833-0.978], p=0.012; females: HR = 0.748 [0.621-0.900], p=0.002) and a BMI ≥25 kg/m² with survival in both sexes (males: HR = 4.282 [1.473-12.446], p=0.008; females: HR = 4.801 [1.182-19.502], p=0.028 with survival in both sexes). Elevated C-reactive protein (CRP) (≥5 mg/L) showed prognostic significance only in males (HR = 4.764 [1.184-19.170], p=0.028). Conclusion:Our findings suggest the possibility of sex-specific patterns in AbE occurrence. Additionally, our analyses identified sex-associated prognostic factors, including the importance of ICI-to-RT interval and BMI in both sexes and the male-specific prognostic value of CRP. These observations warrant further research and consideration in designing personalized RT-ICI combination strategies.

Combining radiotherapy with immune checkpoint inhibitors (RT-ICI) triggers systemic antitumor responses, such as abscopal effects (AbE). Predictors of AbE and its impact on survival in real-world settings remain poorly defined. This multicenter, retrospective cohort study assessed the prevalence of AbE in ICI-refractory progressive metastatic patients by evaluating the additive effect of RT on nonirradiated lesions (NIL). We screened 3773 cases to identify patients with stage IV tumors receiving RT during/after ICI. Abscopal benefit (AB) was defined as abscopal response (AR) or control (AC) by measuring NILs according to iRECIST. AB was observed in 61.3% of 142 included patients and associated with improved median overall survival (18 vs. 8 months, p < 0.01) and progression-free survival (7 vs. 3 months, p < 0.01). Logistic regression identified younger age (OR = 0.951, 95% CI: 0.903-0.995, p = 0.039) and longer ICI-RT intervals (OR = 1.077, 95% CI: 1.019-1.171, p = 0.027) as predictors of AB. There was no association between radiation dose or tumor volume and AB. Cox regression identified BMI ≥ 25 kg/m2 (HR = 3.348, 95% CI: 1.557-7.202, p = 0.002) and CRP ≥ 5 mg/l (HR = 3.058, 95% CI: 1.211-7.724, p = 0.016) as independent negative prognostic factors for survival in this RT-ICI cohort. Median survival was significantly higher among patients receiving ultrahypofractionated RT, compared to other fractions (21 vs. 11 months; p = 0.024). AbE seems to occur reliably and is prognostically relevant in ICI-refractory patients receiving RT. Patient- and timing-related factors were more predictive than RT details in our cohort. Our findings enhance the understanding of tailored RT-ICI approaches and lay the groundwork for targeted radioimmunotherapy strategies and personalized clinical trial designs.

Hepatocellular carcinoma (HCC) represents one of the leading contributors to cancer-related deaths, with the majority of patients diagnosed at stages where curative treatment is no longer possible. Combining stereotactic body radiotherapy (SBRT) with immune checkpoint inhibition (ICI) has gained increasing attention as a therapeutic approach. Beyond its ability to provide high local tumor control (LC), SBRT can provoke immunogenic tumor cell death, promote antigen release and presentation, and modulate the tumor microenvironment in ways that enhance systemic antitumor immunity.In this narrative review, we outline the scientific rationale for integrating SBRT with ICIs, discuss mechanistic and translational findings and summarize results from key clinical trials. The currently available data indicate a synergistic interaction, most notably reflected in improved survival and response rates. Nevertheless, variability in dose and fractionation schedules, treatment sequencing, and patient characteristics complicates interpretation. Well-designed prospective studies are needed to establish optimal protocols and identify predictive biomarkers to guide patient selection.

Introduction:Stereotactic Body Radiation Therapy (SBRT) offers a curative treatment option for patients with early-stage central and ultra-central lung tumours, however can be associated with severe side effects. This review provides a structured quantitative evaluation of outcomes and safety in these critical locations, therefore offering safety-oriented evidence to support individualised treatment planning. Methods:Pubmed/MEDLINE was searched with the term ["Carcinoma, Non-Small-Cell Lung"[Mesh] AND ("Radiosurgery"[Mesh] OR "SABR" OR "stereotactic ablative radiotherapy" OR "SBRT" OR "stereotactic body radiotherapy")] according to PRISMA-guidelines. Trials reporting on SBRT in central and ultra-central lung tumours and on outcome parameters were included. A meta-analysis of proportions was performed using random-effect models. Results:57 retrospective and 12 prospective trials were included, encompassing in total 3,672 and 1,509 patients with central and ultra-central lung tumours. The median follow-up was 22.7 (range: 10.6 - 93.6) months for centrally and 21.2 (8.6 - 93.6) months for ultra-centrally located tumours. For ultra-central lesions the median overall survival was 28.0 (12.0 - 64.5) months compared to 39.4 (19.0 - 57.0) months in central lesions with highest efficacy of SBRT with 60 Gy in 8 fractions. Overall, pooled grade 3-5 toxicity was low for both localizations. The most frequently reported fatal complication in ultra-centrally vs. centrally located tumours was haemorrhage with an estimated proportion of 0.48% [range: 0 - 14.89; CI 95% = 0.00 - 1.68] vs. 0.12% [range: 0 - 7.09; CI 95% = 0.00 - 0.46]. Conclusion:SBRT with 60 Gy in 8 fractions provides a feasible and safe curative treatment approach for patients with centrally and ultra-centrally located lung tumours.

Objective:Increasing evidence suggests that RT and ICI have synergistic effects on anti-tumor immune response, and abscopal responses (AR) have been described more frequently with this combination. Here, we analyzed the frequency and factors associated with AR in NSCLC patients receiving ICI and RT. Methods:In ARTIC (ARO 2022-10, DRKS00032390), a multicenter, retrospective study, patients treated with RT for progressive disease during or after receiving ICI were analyzed for abscopal benefit (AB) and overall survival (OS). Patients were grouped by non-irradiated lesion response; logistic and Cox regression were used to analyze factors linked to AR, AB, and OS. Results:Fifty-six patients from 13 centers with 137 non-irradiated lesions were analyzed. Most received hypofractionated or stereotactic RT. The most common RT sites were lung, bone, and brain. Thirty-three patients showed AB, with 15 patients developing an AR in at least one non-irradiated lesion. In the logistic regression analysis, older age was associated with a higher rate of AP (odds ratio (OR): 1.07, 95%-CI: 1.00-1.14; p = 0.05). Male sex showed a trend towards higher risk of AP (OR = 3.13; 95%- CI: 0.93-11.86; p = 0.075). In the multivariable Cox analysis, ECOG performance score at the start of RT (hazard ratio (HR): 0.29, 95%-CI: 0.12-0.69; p < 0.01) and oligometastatic disease (HR: 0.34, 95%-CI: 0.12-0.94; p = 0.039) were significantly associated with improved OS. Conclusion:RT was able to induce AR in some NSCLC patients who were progressive under ICI, possibly delaying a switch in systemic treatment. AB was less frequent in older patients and in men.

Background Clinician-reported outcomes (CROs) remain a central component of side effect assessment in radiotherapy, while patient-reported outcomes (PROs) are increasingly being integrated into standard practice to better capture the subjective symptom burden experienced by patients. Agreement between CRO and PRO has not been prospectively studied in patients undergoing radiotherapy for brain metastases. Methods NeuroPRO was a prospective longitudinal cohort study enrolling patients receiving radiotherapy for brain metastases. CROs were assessed using predefined CTCAE (version 5.0) items, while PROs were collected using the EORTC QLQ-C30 and BN20 at baseline, end of treatment, and first follow-up. Upon completion of radiotherapy, decision regret was evaluated additionally using the Ottawa Decision Regret Scale. Chance-corrected agreement between CRO and PRO was quantified for each item using Gwet's second-order agreement coefficient (AC2). Longitudinal differences were additionally explored using two-way ANOVA and agreement was further characterized using Bland-Altman analyses with calculation of limits of agreement (LoA). Results Sixty-three patients were included, completing 278 questionnaires and yielding 4448 matched CRO-PRO item comparisons. Across 27 of 32 shared symptoms (84%), PRO scores were higher than CRO scores, indicating systematic symptom underestimation by clinicians. Chance-corrected agreement (Gwet's AC2) was fair to moderate for psychological and neurological symptoms (worry AC2 = 0.30; depression AC2 = 0.39; drowsiness AC2 = 0.44) and substantial to almost perfect for gastrointestinal and treatment-related symptoms (vomiting AC2 = 0.96; seizures AC2 = 0.94; nausea AC2 = 0.92), corroborating the pattern observed with mean-based comparisons. The largest single-item discrepancies were observed for dyspnea (bias 1.00; 95% LoA 0.85–1.14; group p < 0.001), insomnia (bias 0.76; 95% LoA 0.22–1.29; group p < 0.001), and depression (bias 0.75; 95% LoA 0.39–1.12; group p < 0.001). Symptom clustering demonstrated higher agreement for directly treatment-related effects and physical functioning, whereas agreement was substantially lower for emotional and cognitive domains. Patient-reported global health status remained stable after radiotherapy, and decision regret was low. Conclusion Sole clinician assessment systematically underestimates symptom burden in patients undergoing radiotherapy for brain metastases, particularly within psychological domains and somatic symptoms not readily attributable to radiotherapy. These findings reveal a structural perception gap and support the routine integration of PROs into interdisciplinary neuro-oncologic care to enhance symptom recognition and promote patient-centered management (DRKS00031480).

The management of recurrent glioblastoma (rGBM) remains a clinical challenge, with only limited therapeutic options available to date. Reirradiation may offer a progression-free survival (PFS) benefit in selected cases, but data are scarce. Consecutive patients from the last 10 years with GBM (CNS WHO grade 4, IDH-wildtype) who underwent at least one additional course of cranial radiotherapy for suspected or histopathologically confirmed rGBM at a tertiary neuro-oncological center were retrospectively analyzed. The primary endpoint was PFS, secondary endpoints included reirradiation-related adverse event rates, with a particular focus on radiation necrosis (RN). Fifty-nine patients were included with a median follow-up (range) of 8.7 (0.5–48.0) months after reirradiation. The median time to first recurrence was 15 (4–89) months, with the majority occurring in-field (59.7%). The EQD2α/β=10 ranged from 31.3–80.2 Gy with a median prescription dose of 42 Gy. Reirradiation was combined with systemic therapy in 81.4% of patients. No grade 3–5 acute reirradiation-related adverse events were observed. RN was diagnosed in 16.9% of patients (80% grade 2 and 20% grade 3), with a notably low rate in those receiving anti-VEGF therapy parallel to reirradiation. RN risk was independent of reirradiation volume or dose (p = 0.15 and 0.43, respectively). The disease control rate following reirradiation was 83.6% and the median PFS was 5.9 (0.5–48.0) months. Concomitant chemotherapy or anti-VEGF therapy was significantly associated with improved outcomes (p = 0.049), whereas smaller reirradiation volumes demonstrated a non-significant trend towards longer PFS (p = 0.23). In this retrospective analysis, reirradiation for rGBM was feasible and safe, conferring a potential PFS benefit in selected patients. Bevacizumab emerged as a particularly promising combination partner, contributing to both RN prevention and enhanced efficacy.

Objective Stereotactic radiosurgery (SRS) emerges as a non-surgical treatment option for drug-resistant non-neoplastic focal epilepsy. Previous studies have reported that in about 20% of patients treated with radiotherapy, however, subsequent salvage surgery is required, among other because of symptomatic radiation necrosis (RN). We propose a novel and radiobiologically substantiated dose-fractionation regimen which minimizes the RN risk while aiming to preserve efficacy and report our first-in-human experience. Methods From February 2021 to April 2024, three patients (aged 42, 45, and 47 years) with different underlying etiologies were treated, including a post-hemorrhagic lesion, Rasmussen encephalitis, and focal cortical dysplasia. We applied linac-based frameless fractionated stereotactic radiotherapy (fSRT) to a total dose of 50 Gy in 10 fractions over 2 weeks. Each epileptogenic zone was defined by a multidisciplinary team, including a radiation oncologist, epileptologist, neurosurgeon, and neuroradiologist. Results The irradiated volumes were 10.3, 11.3, and 16.5 cm 3 . After a follow-up of 12, 29, and 36 months, all three patients experienced an improvement in both seizure frequency and severity (two already during or shortly after fSRT). One patient achieved complete seizure freedom. All patients reported improvements in quality of life and regained independence or displayed functional recovery. Tolerability was excellent, with radiation-induced side effects being mild (grade 1 only) and transient. RN was not observed. One patient died 29 months after radiotherapy most likely from a ruptured aneurysm of a vertebral artery, unrelated to the treatment. Significance Frameless fSRT of 50 Gy in 10 fractions was feasible and might be safe and effective in selected patients with drug-resistant non-neoplastic focal epilepsy and large suspected epileptogenic zones. A prospective single-arm evaluation with structured long-term follow-up including assessment of patient-reported outcome measures is currently being conducted.

In recent years, intraoperative radiotherapy (IORT) with low-energy X-rays is emerging as an alternative to postoperative stereotactic radiotherapy (SRT) of the resection cavity in patients with resectable brain metastases (BMs). We performed a systematic review of the MEDLINE, Embase, and Scopus databases, including all original articles on IORT for resectable BMs from 2015−2025. Data on safety, local control, and survival outcomes were collected. Ten records (5 prospective single-arm trials) were included, representing 261 patients (49% lung primary) with a median follow-up (range) of 14 (0−79) months. 77% of patients had a solitary BM at the time of surgery and IORT. The median applicator size was 2.0 cm and the median prescribed dose (range) 22.3 (20−30) Gy. The 1-year local control rate was 93% and the 1-year distant brain control rate 48%. Median overall survival was 19 months. Only 6% of patients developed leptomeningeal disease and the cumulative rate of radiation necrosis was 2.6% (grade 1 in 56% of cases). The median time to next treatment (range) was 31 (1−136) days. This was significantly shorter compared to SRT control collectives. IORT for patients with BMs has a favorable toxicity profile and yields excellent local control. A potential advantage is the rapid completion of interdisciplinary BM treatment, allowing a swift transition to subsequent cancer treatments. A planned registry and a prospective randomized phase 3 trial will establish the preferred radiotherapy modality in the context of resectable BMs.

Purpose Stereotactic radiosurgery (SRS) yields excellent local control in patients with a limited number of brain metastases (BMs), but radiation-induced cerebral edema and radiation necrosis (RN) in particular pose as a dose-limiting late toxicity, with the same holding true after fractionated radiotherapy for glioma. In symptomatic patients, the first-line standard of care includes corticosteroids, which may, however, be counterproductive in the evolving era of immunotherapy. Boswellic acid (BA), available as an over-the-counter dietary supplement, has been suggested as a potential corticosteroid-sparing alternative due to its anti-inflammatory and anti-angiogenic effects. Methods We performed a comprehensive literature search of the MEDLINE, Embase, Scopus, and Cochrane databases, identifying publications reporting on the use of BA during or after brain irradiation in humans. Using the RAMESES framework, relevant data are summarized using a meta-narrative approach. Results Six records (three for edema reduction in large irradiated volumes and three for RN after SRS) were identified, encompassing 130 patients. Roughly half of patients benefited from BA (radiographically or clinically) and about one-third could successfully taper dexamethasone or prevent its long-term intake. Tolerability of BA was favorable, with mild gastrointestinal discomfort being reported most frequently. Current drawbacks include unknown optimal formulation as well as timing and dosing, a considerably large number of required daily capsules, and uncertain interactions with other drugs. Conclusion Overall, the clinical evidence on the use of BA for radiation-induced cerebral edema and RN is lacking and well-designed prospective trials are warranted to further investigate this potential low-cost corticosteroid-sparing option.

Radiation dermatitis (RD) is the most common side effect of breast irradiation, yet only few potent preventative and therapeutic options are available. Following encouraging results from a phase 1 and 2 trial on the topical use of non-invasive physical plasma (NIPP), a very well-tolerated physical treatment option to promote tissue regeneration generated from ambient air, we now present the study protocol for a planned phase 3 trial. In this randomised double-blind placebo-controlled trial, patients with breast cancer will be randomised (1:1) to receive either 120 s of NIPP or sham treatment with an identical device daily during hypofractionated breast irradiation following breast-conserving surgery. Standard skin care with urea lotion will be applied twice daily to the whole breast by all patients. Acute skin toxicity will be assessed weekly and includes clinician- (CTCAE v5.0) and patient-reported (modified RISRAS), and objective (spectrophotometry) assessments. The trial has started enrolment in the first quarter of 2024 and is projected to recruit 140 patients over 36 months. This randomised controlled trial will recruit a homogeneous patient collective in terms of RD risk and aims to unequivocally establish the impact of NIPP on RD by employing a robust trial design, incorporating both the patient’s perspective and validated objective outcome measures. If the addition of NIPP proves useful, it might reduce both physical and psychological distress caused by RD in numerous breast cancer patients and beyond. German Clinical Trial Registry DRKS00032560 (January 9th 2024).

The increasing importance of radiation oncology (RO) education worldwide drives a need for modernization of university curricula, particularly in anticipation of the new Licensing Regulation for Physicians (Ärztliche Approbationsordnung, ÄApprO) in Germany. This study evaluates RO education at four German medical schools and compares student perspectives with the recommendations of the academic radiation oncology consortium of the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) in order to highlight gaps and opportunities for curriculum improvement. A cross-sectional survey was conducted among medical students from the universities in Aachen, Bonn, Cologne, and Düsseldorf (ABCD) from January to June 2022. The standardized digital questionnaire included 31 questions (Likert scale and open-ended items) assessing teaching quality, learning formats, and practical relevance. Descriptive and thematic analyses were performed. A total of 152 fully completed surveys were analyzed. Most students (76

INTRODUCTION:Linac-based SRS provides a highly precise noninvasive treatment option for intracranial lesions. DCA and VMAT are commonly used Linac-based techniques. There are no standardized guidelines for technique selection, particularly considering the geometric properties of the lesions. We thus sought to compare DCA and VMAT to define a workflow for clinical decision-making. This study introduces Qasym, a novel parameter quantifying lesion asymmetry, and compares the dosimetric performance of DCA and VMAT. MATERIALS AND METHODS:Between 2018 and 2021, a total of 89 brain metastases from 24 patients with lesion volumes up to 4.3 cm3 were included. VMAT and DCA plans were created for each lesion with identical field parameters, resulting in a total of 178 evaluable plans. The parameters included the CI, DSI, and MUs. Various approaches for quantifying asymmetry were explored and their impact on CI and DSI was investigated. Additionally, we introduced the novel Qasym index, designed to quantify lesion asymmetry. RESULTS:VMAT resulted in lower CI values, especially for volumes exceeding 2 cm3. With a prescription dose of 20 Gy, DSI90% values were comparable between VMAT and DCA for < 2 cm3, while VMAT achieved lower values for larger volumes. VMAT showed higher DSI50% and DSI25% values for < 2 cm3, which reversed for larger volumes. V2Gy values were similar for both techniques for < 2 cm3 but were lower for VMAT in larger volumes. Qasym significantly correlated with CI (p < 0.01). Analysis of ΔCI% and ΔDSI% revealed that VMAT outperformed DCA for lesions > 2 cm3 and smaller volumes with a Qasym > 1.2. DCA required significantly fewer MUs (p < 0.01). CONCLUSION:This study provides detailed dosimetric information on two commonly applied planning techniques for Linac-based SRS treatment for brain metastases. These findings might support decision making for optimal technique selection upon volumetric features. Qasym provides a practical tool for these purposes.

Purpose:The role of radiotherapy in the context of limited liver metastases is emerging rapidly with a variety of available technical approaches. Here, we provide a dosimetric comparison of three different radiotherapy modalities for non-resected liver metastases. Methods:This multicentric study included 30 patients previously treated for solitary liver metastases. Interstitial high dose-rate brachytherapy (HDR), stereotactic body radiation therapy (SBRT), and kilovoltage electronic brachytherapy (eBT) with a single dwelling point, as an in this context novel modality, were planned with a 25-Gy single fraction and dosimetrically compared. The primary endpoint was difference in healthy liver tissue exposure. Secondary endpoints included target volume coverage, dose to the surrounding organs at risk (OARs), and radiation treatment time. Results:The median (range) lesion volume was 9.3 (2.5 - 29.7) cm3. Electronic BT yielded a significantly better OAR dose sparing compared to SBRT. Radiation exposure to the healthy liver was significantly lower with eBT (V9.1 Gy 13.8 [3.4-41.6] cm3) and HDR (49.2 [12.7-116.8] cm3) when compared with SBRT (98.8 [54.3-303.7] cm3; p < 0.001 for both). Mean treatment time was shortest for SBRT (6.1 min vs. 7.8 min for HDR [p = 0.003] vs. 16.1 min for eBT [p < 0.001]). Equally, CTV D90% and D95% were superior for SBRT (p < 0.001 vs. HDR and eBT). Conclusion:Minimally invasive single-catheter eBT provides a new potential approach in the context of unresectable liver metastases, with optimal OAR dose sparing, yet suboptimal target volume coverage. Combining the advantages of both modalities, a multi-dwelling eBT approach as in HDR might ease applicability in clinical routine with optimized target coverage while maintaining excellent OAR doses. Future prospective investigations are required to further define its role within well-established liver-directed therapies.

BACKGROUND:Abscopal effect (AbE), the regression of non-irradiated metastatic lesions (NILs) following radiotherapy (RT), is relevant in patients with malignant melanoma (MM) with progressive disease (PD) under immune checkpoint inhibition (ICI) as resistance to immunotherapy. In the "ARTIC" trial, we assessed the incidence of AbE in patients with progressive MM by evaluating the effect of RT on NILs. METHODS:ARTIC (Abscopal effects in metastasized cancer patients treated with RadioTherapy and Immune Checkpoint inhibition) (ARO (Arbeitsgemeinschaft Radiologische Onkologie) 2022-10, DRKS00032390) retrospectively screened clinical records of patients with stage IV MM with PD under ICI. Patients received RT for metastases and had ≥1 NIL outside the RT field (=control lesion). NILs were evaluated according to iRECIST (immune Response Evaluation Criteria in Solid Tumors): abscopal response (AR): size reduction ≥30%, abscopal progression (AP): size increase ≥20%, abscopal control (AC): all others. Patients with AR and/or AC were categorized as abscopal benefit (AB), patients with AP and/or mixed response=no AB. RT details and factors influencing AR were analyzed. RESULTS:After screening clinical records of 3773 patients with stage IV tumor from 12 oncological centers in Germany, we identified 47 patients with MM with 115 NILs. RT targeted metastases in brain (38.3%) and lung (19.1%), primarily using stereotactic RT (29.8%). The mean time interval between the end of ICI and RT was 3.53±5.67 months. AR was achieved in 19.1% of patients and 29.1% of lesions. Compared with stereotactic RT, normofractionated or other (non-stereotactic) RT regimens significantly reduced the probability of AB (OR=0.092, p=0.04, 95% CI: (0.007 to 0.758)). Longer ICI-to-RT intervals were associated with reduced mortality risk (HR=0.703, p=0.007, 95% CI: (0.544 to 0.908)). Patients with AB had a longer median overall (17 vs 9 months) and a longer median progression-free survival (4 vs 2 months). CONCLUSIONS:RT can induce AR in patients with MM with PD under ICI, particularly with hypofractionated regimens and long ICI-to-RT intervals. Our findings can serve as a reference for designing prospective trials.