BACKGROUND/AIM:In patients irradiated for high-risk prostate cancer, bladder volumes should be ≥200 ml to reduce the risk of radiation cystitis. A prospective trial evaluates a reminder app to increase bladder filling during irradiation without pelvic lymph nodes (LN). This retrospective study investigates whether patients irradiated with LN can also be included in that trial. PATIENTS AND METHODS:Forty patients irradiated with (N=17, group A) or without (N=23, group B) pelvic LN and presenting with a pre-irradiation bladder volume <200 ml were analyzed regarding fractions with a bladder volume <200 ml. RESULTS:Mean numbers of fractions with a volume <200 ml in the entire cohort, group A, and group B were 29.0±7.0, 28.8±7.6, and 29.2±6.6, respectively. The difference between groups A and B was not significant (p=0.978). CONCLUSION:Irradiation of pelvic LN had no significant impact on the number of fractions for bladder volumes <200 ml. Patients irradiated with LN may be included in the prospective trial.

Background/Aim: Patients irradiated for breast cancer may experience acute skin toxicity. To reduce this risk, a mobile application was created which reminds patients to carry out skin care. Before using this app in patients, a pre-study evaluating its usability in healthy volunteers was required. Patients and Methods: In this prospective study, 30 healthy volunteers from Germany and Denmark were asked to test the app and complete a questionnaire including ten statements ("yes or "no") in three sections. Results: Satisfaction rates (statements affirmed with "yes") were 66.7% (18/27 participants) and 78.6% (22/28) in the section "download and installation", and 100% (29/29) and 96.7% (29/30) in the section "navigation". In the section "content/functions", the six statements were addressed by 28-30 participants; satisfaction rates were 86.7% to 100% (median 96.5%). Dichotomous responses were supplemented by individual comments. Conclusion: This study revealed that the reminder app needed improvement before tested in patients and demonstrated the importance of a pre-study in healthy volunteers.

Malignant spinal cord compression (MSCC) is a serious complication of spinal metastases and primary spinal tumours that can severely affect quality of life and overall survival. Clinical trials have used inconsistent definitions, criteria, and endpoints, limiting comparability. We conducted a Delphi consensus process following a systematic review of prospective MSCC trials from Jan 1, 2003, to Feb 26, 2024. From June 25, 2024, to Jan 11, 2025, experts from 20 countries participated in two survey rounds, 74 in round 1 and 71 in round 2. Consensus was defined as over 75% agreement. 49 statements reached consensus, including definitions for clinical, radiological, and impending MSCC using the Bilsky scale. Experts agreed on baseline and follow-up assessments, including pain, motor and sensory function, ambulation, and urinary and anal sphincter function. Standardised functional scales, response criteria, endpoint definitions, and timing of assessments were established. A core set of mandatory and secondary endpoints was defined for different MSCC scenarios, along with minimum reporting standards for surgery and radiotherapy toxicity. These recommendations aim to standardise future MSCC trials and audits to improve data consistency and comparability.

BACKGROUND/AIM:Radiotherapy for lung cancer can lead to significant fatigue and a decrease in physical activity. An app that reminds the patients several times per day to perform a certain number of steps may be helpful in this respect. Such an app has just been developed. We aimed to investigated the functionality and practicability of the app in healthy volunteers before testing it in a prospective clinical trial. PATIENTS AND METHODS:Thirty healthy volunteers participated in this prospective study (APPAREL-HV) and evaluated the app by affirming (=satisfaction) or negating ten statements in three sections related to functionality and practicability. If the satisfaction rate was <80%, the app required further optimization. If it was <60%, it appeared not useful. Subgroup analyses were performed for iPhone vs. Android users, German vs. Danish participants, and younger (<50 years) vs. older (≥50 years) patients. RESULTS:Overall satisfaction rates were 86.7% (two statements), 93.3-100% (two statements), and 90.0-100% (six statements) in the sections Download and installation, Navigation, and Content/functions, respectively. Android users were significantly less satisfied with Download and installation (50.0% vs. 95.8%, p=0.018). Otherwise, satisfaction rates were always ≥80%, and subgroup analyses showed no significant differences between the groups compared. CONCLUSION:According to the results of the APPAREL-HV, the current version of the app appeared not sufficiently useful for Android users and required significant improvement for this subgroup in the section Download and installation.

BACKGROUND/AIM:Many patients with prostate cancer receive moderately hypo-fractionated radiotherapy (mHF-RT). Inappropriate bladder filling during the mHF-RT course increases urinary toxicity. This study investigated the impact of pre-RT bladder volumes on the subsequent filling status. PATIENTS AND METHODS:One-hundred-and-nineteen prostate cancer patients irradiated with mHF-RT (60 Gy in 20 fractions) were included in this retrospective study from three European countries. The impact of pre-RT bladder volumes on the number of fractions with a volume <200 ml was examined. RESULTS:In case of a pre-RT bladder volume <200, <250, and <300 ml, the corresponding mean number of fractions with a bladder volume <200 ml during mHF-RT was 16.6 (±5.0), 15.9 (±5.6), and 15.1 (±5.9), respectively. The impact of the pre-RT volume (<200 vs. ≥200 ml, <250 vs. ≥250, <300 vs. ≥300 ml) on the number of fractions with a volume <200 ml was always highly significant (p<0.0001). CONCLUSION:Pre-RT bladder volumes <200 ml, <250 ml, and <300 ml were significantly associated with higher numbers of bladder volumes <200 ml during mHF-RT. These findings will lead to an amendment to a prospective trial.

BACKGROUND/AIM:Patients receiving radiotherapy for lung cancer may experience treatment-related adverse effects that reduce physical activity. Smartphone-based reminder applications may help patients maintain daily activity; however, information on changes in step counts during radiotherapy is limited. The APART-LUNG study investigated changes in physical activity between the first and fifth weeks of radiotherapy and explored potential factors associated with decreased activity. PATIENTS AND METHODS:Twenty patients were enrolled, of whom 19 were eligible for analysis. Physical activity was assessed as the weekly mean number of steps per smartphone wear-hour during weeks 1 and 5 of radiotherapy. The primary endpoint was the within-patient difference between week 5 and week 1. Associations between changes in step counts and age, sex, performance status, comorbidity, body-mass index, histology, and concurrent systemic treatment were explored. RESULTS:The mean numbers of steps per wear-hour were 344.3±171.6 in week 1 and 363.5±189.9 in week 5. Median values were 318.4 (range=123.3-762.9) and 300.3 (range=108.3-704.7) steps, respectively (p=0.465). The weekly average number of steps per wear-hour decreased in nine patients, increased in nine patients, and remained almost constant (plus three steps) in one patient. No characteristic was significantly associated with a decrease in steps. The greatest difference regarding the proportion of patients with a decrease in steps was observed for concurrent systemic treatment (no vs. yes, difference=37%). CONCLUSION:In this pilot study, step counts did not significantly decrease during radiotherapy for lung cancer. No investigated characteristic was significantly associated with decreased physical activity, although concurrent systemic treatment showed the strongest signal and should be considered in the design of future prospective trials.

Background/Objectives: Squamous cell carcinoma of the nasal vestibule (SCCNV) represents a rare malignancy traditionally managed by radical surgical resection, frequently at the cost of substantial functional impairment and disfiguring aesthetic consequences. This study investigates an organ-preserving therapeutic strategy integrating high-dose-rate interventional radiotherapy (HDR-IRT; brachytherapy) with organ-preserving surgery. Material and Methods: A retrospective analysis of patients with primary SCCNV treated using HDR-IRT between 2008 and 2022, excluding recurrent disease and cutaneous squamous cell carcinomas. Interstitial HDR-IRT catheters were implanted intraoperatively, with radiation delivered twice daily to a target volume encompassing the tumor and a 10-15 mm safety margin. Results: Fifty-one patients were included, with a median age of 71 years. The median total dose was 40 Gy. Gross total resection was performed in 7 patients, and subtotal resection in 44. The median follow-up was 35 months. The 5-year nose preservation rate was 90%, with local control at 84%, regional failure-free survival at 94%, and overall survival at 82%. In total, 49 acute toxicity events were documented, including two grade 3 events, while 35 chronic toxicity events were reported, including one grade 3 event. At 3 years, 84.3% of cosmetic outcomes were rated as satisfactory, 9.8% as acceptable, and 5.9% as unsatisfactory. Conclusions: The OSIRIS approach, combining HDR-IRT with organ-preserving surgery, is an effective treatment for SCCNV, offering high organ preservation and favorable long-term disease control, with manageable toxicity and positive cosmetic outcomes.

Background/Objectives: Patients with breast cancer undergoing chemotherapy with taxanes or platin derivates often develop peripheral neuropathy (CIPN). Higher-grade CIPN generally affects the patient’s quality of life. Because the treatment options for CIPN are limited, early diagnosis is desirable to allow for timely modifications of the treatment. This may be facilitated with scoring tools that are ideally usable by the patients. A prospective study suggested that a recently developed self-assessment tool might be able to reveal the difference between the absence of CIPN and higher-grade CIPN. When CIPN has reached an advanced grade, alteration of the chemotherapy regimen may have only a limited effect. Therefore, it is important to know whether the new scoring tool can identify CIPN even when it is still mild. The current trial (NCT07604441) aims to identify the optimal cutoff point value for detecting mild CIPN. Given the limited sample size, the derived cutoff will be considered preliminary and will require validation in a larger independent cohort. Methods: The NEURO-BREAC-02 trial aims to identify the optimal cutoff point value of the new tool to distinguish between absent and mild CIPN after treatment with taxanes for breast cancer. Scores ranging between 0 and 44 points are reported via self-assessment supported by a neuropathy tracker. Secondly, the satisfaction of participants with the self-assessment tool is evaluated. Twenty-six participants (19 with mild CIPN and 7 without CIPN) are required, and 28 must be enrolled. Conclusions: The outcomes of the NEURO-BREAC-02 trial are considered crucial for the creation of a self-assessment tool to identify mild CIPN in patients with breast cancer and are a necessary addition to the preceding NEURO-BREAC study.

BACKGROUND:Stereotactic body radiation therapy (SBRT) is increasingly used for bone metastases, but inconsistent endpoint definitions and reporting hinder evidence synthesis and clinical application. This study aimed to establish international consensus recommendations for standardised endpoints, definitions, and reporting parameters in SBRT studies for bone metastases. METHODS:A systematic review of prospective SBRT studies (2014-2024) informed a three-round modified Delphi consensus process conducted from 2024 to 2025. Consensus was predefined as at least 75% agreement. Candidate items were refined through iterative online surveys, qualitative feedback, and a final prioritisation vote by an international multidisciplinary expert panel. RESULTS:Of 114 invited experts, 82 from 20 countries participated in at least one Delphi round. Review of 58 prospective studies showed substantial variability in endpoint definitions, pain and toxicity assessment, radiological response criteria, and timing of outcome evaluation. The panel endorsed 46 reporting items (41 required, 5 recommended) and prioritised core endpoint sets across three clinical contexts: oligometastatic, oligoprogressive, and asymptomatic high-risk bone metastases. Strong consensus was reached for definitions of vertebral compression fracture (92%), time to salvage local therapy (93%), duration of pain response (92%), and time to local progression (90%); pain flare achieved 89% agreement. A revised clinical response framework (C-BRAC), introducing a stable disease category, achieved 91% agreement and was recommended for exploratory use alongside existing criteria. CONCLUSIONS:These recommendations provide a structured framework for designing and reporting SBRT studies in bone metastases and may improve consistency, comparability, and future guideline development.

Background Malignant spinal cord compression (MSCC) is one of the most devastating complications in cancer patients. This retrospective single-center analysis was aimed to identify prognostic factors for better functional outcome after radiotherapy for MSCC. Patients and methods Consecutive patients with MSCC treated with upfront radiotherapy between January 2017 and December 2022 were included in this analysis. Data on patient, tumor and treatment characteristics, functional status before and after treatment and diagnostic work-up were collected from the hospital digital database. The treatment was considered effective if performance status (PS) was maintained in PS 1-2 patients or PS improved in PS 3-4 patients. Results 295 patients were treated for MSCC. The most common primary tumor type was lung cancer (29.3%), followed by prostate (18%) and breast cancer (12%). The treatment was effective in 44.7% of patients. Patients who survived more than 1 month after radiotherapy were more likely to experience functional improvement than patients who died within the first month (60.5% vs. 16.5%, p < 0.001). In the multivariate analysis PS 1-2, myeloma/lymphoma, MRI at the time of MSCC and no motor deficits vs. paralysis were associated with better functional outcome. Conclusions The prognosis of patients with MSCC remains poor. Better stratification of patients to assess possible benefit of radiotherapy for MSCC is warranted.

Background/Objectives: A considerable number of patients with malignant spinal cord compression (MSCC) and a longer expected lifespan do not receive upfront surgery but radiation therapy alone. These patients were suggested to benefit from radiation programs with total doses > 30 Gy in terms of better local progression-free survival (LPFS). A previous study compared such regimens, namely 15 × 2.633 Gy over three weeks (34 patients, prospective cohort) and 20 × 2.0 Gy over four weeks (239 patients, control), using a propensity score-adjusted approach. Both regimens were associated with similar rates of overall survival (OS) and LPFS. However, follow-up was limited to 12 months. For long-term survivors, a longer period of follow-up would be desirable. Therefore, the present study was initiated. Methods: Retrospective collection of additional data enabled us to provide OS- and LPFS-rates at 36 months following radiation therapy. Results: In the prospective cohort, 36-month rates of OS and LPFS were 27.0% and 89.7%, respectively. After application of the propensity score-adjusted Cox regression model, 36-month OS-rates (HR 1.454; 95% CI 0.748-2.828; p = 0.270) and LPFS-rates (HR 0.311; 95% CI 0.041-2.352; p = 0.258) appeared not considerably different. Late radiation myelopathy and pathologic vertebral fractures were not identified. Conclusions: The results of the current study suggest that the role of 15 × 2.633 Gy should be further investigated in selected patients with MSCC, particularly when considering its shorter overall treatment time in comparison to 20 × 2.0 Gy. Overall, our findings are hypothesis-generating rather than confirmatory.

BACKGROUND/AIM:The risk of genitourinary toxicity during radiotherapy for prostate cancer was found to be lower for bladder volumes ≥200 ml. An app that reminds patients daily to drink water might be helpful. Before being investigated in patients, an app should be tested in healthy volunteers. MATERIALS AND METHODS:Thirty healthy volunteers were included in this prospective study and asked to test the app and affirm (=satisfaction) or negate nine statements. These statements belonged to the sections 'Download and installation' (two statements), 'Navigation' (two statements), or 'Content/functions' (five statements). If a satisfaction rate was <60%, the app was to be considered not useful. If it was <80%, the app needed optimization. iPhone users (n=18) were compared to Android users (n=12). RESULTS:Satisfaction rates (participants affirming a statement) were 90.0% (27 out of 30 participants) and 86.7% (26 out of 30 participants) regarding the two statements belonging to the Download and installation section. Regarding the two statements of the Navigation section, satisfaction rates were 100% (28 out of 28) and 96.6% (28 out of 29), respectively. For the Content/functions section, satisfaction rates were 79.3% (23 out of 29 participants) for the statement: "The app reminded me at the selected times". For the other four statements, satisfaction rates were each 100% (25 out of 25, 27 out of 27, 28 out of 28, and 29 out of 29 participants). Significant differences between iPhone and Android users were not observed. When looking at the subgroups of iPhone and Android users, two additional aspects were identified that needed modifications. CONCLUSION:Although the new reminder app was mainly rated usable, some modifications were required. Our findings highlight that a pre-study in healthy volunteers is important.

Background Patients' expectations correlate with outcomes. Yet little is known about multidimensional expectations and associated factors among patients with cancer awaiting radiotherapy. Methods We conducted a cross-sectional survey to explore expectations and associated factors based on the Likert-type Treatment Expectation Questionnaire (TEX-Q) among patients with cancer awaiting radiotherapy. The TEX-Q mean (higher score = more positive overall expectations) was the primary outcome. Secondary outcomes included the TEX-Q Treatment benefit (higher score = more beneficial expectations) and Adverse events (higher score = worse adverse events expectations) subscales. TEX-Q scores range from 0 to 10. We performed univariate and multivariate analyses (MVA). Results Among 368 eligible patients, 140 participated and 133 were analysable. The median age was 67.5 years (interquartile range: 18.8) and the female-male ratio was 1:1. The TEX-Q mean value was 7.0 (SD:1.8), the Treatment benefit mean was 8.6 (SD:1.7), and the Adverse events mean was 4.3 (SD:2.3). Treatment benefit and Adverse events expectations did not correlate. On MVA, overall expectations were worse among patients living alone (p = 0.01), with higher education (p < 0.001), and receiving concomitant chemotherapy (p = 0.048). Treatment benefit expectations were worse among patients with higher education (p = 0.03) and with palliative/unknown intent (p = 0.003). Adverse event expectations were more pronounced among patients living alone (p = 0.01), inpatients (p = 0.04) and more distressed patients (p = 0.01). Conclusions Patients' expectations were favourable overall. Patients living alone, treated with palliative intent and at more distress expected worse outcomes which may require adapted communication strategies or supportive measures. Future longitudinal studies should investigate expectation-outcome pairings and interventions to realistically improve patients' expectations regarding radiotherapy.

Background:The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for bone metastases 22 (EORTC QLQ-BM22) is a site-specific health-related quality-of-life instrument for patients with bone metastases. However, modern treatments and extended survivorship have introduced new toxicity profiles and clinical challenges. We systematically assessed the measurement performance of QLQ-BM22 to determine if contemporary evidence supports updating the module. Methods:A search was conducted using Medline, Embase, and Cochrane Central Register of Controlled Trials from inception to November 7, 2025. Two independent reviewers screened English-language articles reporting on the development, psychometric evaluation, or clinical application of the QLQ-BM22. Data regarding reliability, validity, responsiveness, and feasibility were extracted and synthesized. Studies using the module solely as an outcome measure without psychometric data were excluded. The review protocol was registered with PROSPERO (CRD420251052602). Findings:49 publications were included. While available in 32 language versions, clinical use was identified in at least 16. Internal consistency was generally high (Cronbach's α > 0·70), although variability was observed in the Painful Sites subscale (range α = 0·34-0·93). Test-retest reliability was excellent (intraclass correlation coefficient >0·90). Construct validity was supported by weak correlations (r < 0·40) with unrelated domains in the EORTC core questionnaire, confirming the module's divergent validity. Item-level missingness was generally low in completed questionnaires, although follow-up completion was more variable in longitudinal studies. Responsiveness was strongest in palliative radiotherapy settings, whereas evidence in surgical and systemic therapy settings remains limited. Interpretation:While psychometrically sound, the reliance of QLQ-BM22 on historical validation data, limited cross-cultural validation, and inconsistent reliability in the Painful Sites subscale warrant an update. A modernized module is needed to capture contemporary symptom profiles, standardize cross-cultural measurement, and reduce burden. Funding:This research was funded by the EORTC Quality of Life Group, grant number 005/2023.

Background:Diffuse intrinsic pontine glioma (DIPG) remains uniformly lethal. Stereotactic biopsy confirms the diagnosis and enables molecular profiling. Metastasis along the biopsy track (BTM) has been reported only anecdotally; its prevalence, clinical relevance, and implications for treatment remain unclear. Methods:A multicenter retrospective study in patients with confirmed DIPG and BTM was conducted based on central neuroradiologic review. Radiotherapy schedules were re-assessed to evaluate the feasibility of upfront biopsy track irradiation. Results:Ten children met inclusion criteria (median age 6.8 years). Biopsy route was supratentorial in six and infratentorial in four children, and side-cutting needles were used predominantly. H3F3A mutations were most frequent (n = 8); TP53 alterations were common in tumors with extended molecular profiling available. Median PFS was 8.1 months. Five patients each developed BTM prior to (median 2.7 months) or concurrently with progression of primary tumor. There was no difference in overall survival (median OS 12.0 months) compared with the reference cohort. Estimated BTM prevalence among biopsied DIPG from additional registry data was between 6.9% and 13.0%. Primary biopsy track irradiation proved to be feasible, and comparing the surgical access routes, the infratentorial biopsy track hardly increased radiation exposure of the whole brain. Conclusions:Needle track metastasis is a rare progression pattern in stereotactic biopsied DIPG. Upfront irradiation of the biopsy track may represent a strategy to mitigate the potential risk of BTM. From a dosimetric perspective, an infratentorial approach may therefore be considered, as it was associated with only marginally increased radiation exposure.

Despite the increasing popularity of upfront decompressive surgery, there are still patients with malignant spinal cord compression (MSCC) and expected longer-term survival receiving irradiation alone. In these patients, local progression-free survival (LPFS) may be improved with doses beyond the commonly applied regimen of 10 × 3.0 Gy. A prospective phase 2 trial (RAMSES-01) investigated the benefit of two regimens, 15 × 2.633 and 18 × 2.333 Gy, compared with a 10 × 3.0 Gy (historical control). Patients in the phase 2 cohort had significantly better local progression-free survival (LPFS) after 1 year. Since recurrent MSCC-related motor weakness is a serious situation, it must be avoided as long as possible. In this respect, it is important to know whether the superiority of 15 × 2.633 and 18 × 2.333 Gy found in the RAMSES-01 trial still exists after 2 or 3 years. This led to the current study. In the phase 2 group, 2- and 3-year LPFS rates were 93.1% and 93.1%, respectively, and survival rates were 54.2% and 36.1%, respectively. According to propensity-adjusted Cox regression analyses, radiotherapy regimens in the phase 2 cohort resulted in significantly better LPFS at 2 (p = 0.017) and 3 (p = 0.013) years. In contrast, survival was not significantly different (p = 0.251 and p = 0.288, respectively). Radiation myelopathy and pathologic vertebral fractures were not observed in any group. Given the limitations of this study, irradiation 15 × 2.633 or 18 × 2.333 Gy may be an alternative option for patients with MSCC and longer expected survival treated with irradiation alone.

Hypoxia is an important hallmark of the tumor microenvironment (TME) in solid tumors and is closely associated with resistance to radiotherapy and a poorer clinical outcome. Tumor-associated plasma-derived small extracellular vesicles (sEVs) have gained increasing attention as an important regulatory TME component for tumor progression and immune evasion. This study aimed to investigate the involvement of plasma-derived sEVs from head and neck squamous cell carcinoma (HNSCC) patients in the systemic regulation of hypoxia-related molecular pathways in circulating immune cells. Plasma-derived sEVs of healthy donors (HDs) and HNSCC patients were isolated and evaluated for morphology, size, miRNA cargo composition, and their influence on monocyte characteristics. Transfer of plasma-derived sEVs from HNSCC patients stimulated increased levels of checkpoint molecule PD-L1 and chemokine CXCL4 secretion. An accumulation of hypoxia-inducible factor (HIF)-2α was associated with hypoxia-regulating miRNAs in sEVs from HNSCC patients. This provides new insights into a proposed tumor-associated systemic sEV-miRNA-mediated hypoxia transfer.