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Background: Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population., Methods: This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5-10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5-15 fractions. Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here). This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment. The safety population comprised patients who received the study intervention at least once after randomisation. The study is registered with ClinicalTrials.gov, NCT04134598, and is ongoing and actively recruiting., Findings: Between March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n=365) or endocrine therapy (n=366). This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9-24·2). Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0-80·0) in the radiotherapy group and 74·0 years (72·0-80·0) in the endocrine therapy group. 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment. The mean baseline GHS score was 71·9 (SD 19·1) in the radiotherapy group and 75·5 (19·3) in the endocrine therapy group. At 24 months, the age-adjusted, G8 score-adjusted mean change from baseline in GHS was -3·40 (95% CI -7·82 to 1·03; p=0·13) in the radiotherapy group and -9·79 (-14·45 to -5·13; p<0·0001) in the endocrine therapy group, with an adjusted mean difference of 6·39 (0·14 to 12·65; p=0·045) favouring radiotherapy. Treatment-related adverse events were less frequent in the radiotherapy group (65 [67%] of 97 patients) compared with the endocrine therapy group (76 [85%] of 89). The most common grade 3-4 adverse events were arthralgia (six [7%] of 89 in the endocrine therapy group vs 0 of 97 in the radiotherapy group), pelvic organ prolapse (three [3%] vs 0), fatigue, hot flashes, myalgia, bone pain, and fractures (two [2%] vs 0 for each). Serious adverse events were reported in 15 (15%) patients in the radiotherapy group and 13 (15%) in the endocrine therapy group. There were no treatment-related deaths in either group., Interpretation: Endocrine therapy was associated with a greater reduction in HRQOL, as measured by GHS, compared with radiotherapy at 24 months. While these interim results suggest radiotherapy might better preserve HRQOL in older women with low-risk early breast cancer, further data on disease control outcomes and final patient accrual are needed to draw definitive conclusions., Funding: Fondazione Radioterapia Oncologica., Competing Interests: Declaration of interests IM has received occasional fees for advisory board participation supported by Eli Lilly, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, and Menarini StemLine, outside the submitted work. ML has reported advisory roles supported by Roche, Eli Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini StemLine; speaker honoraria from Roche, Eli Lilly, Novartis, Pfizer, AstraZeneca, Takeda, Ipsen, Sandoz, Libbs, Knight, Daiichi Sankyo, Gilead, and Menarini StemLine; and travel grants from Gilead, Daiichi Sankyo, and Roche. VS has reported honoraria from Nucletron and Elekta. TS discloses unrestricted grants for programmes of Europa Donna Slovenia, as well as speaker honoraria from Pfizer, MSD, Roche, and AstraZeneca. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Radical cystectomy (RC) is considered the standard treatment for muscle invasive bladder cancer (MIBC). However, RC is often burdened by significant impact on quality of life (QoL); Continence preserving methods (e.g., continent cutaneous urinary diversion and orthotopic neobladder-ONB), have been proposed as alternatives to improve postoperative QoL. Trimodal therapy (TMT) emerged as alternative to surgery. To assess the impact of these treatments from the patients' perspective, we undertook a systematic review and meta-analysis of literature, focusing on studies reporting QoL data about each of the abovementioned approaches. A systematic review was carried out including all prospective and retrospective studies enrolling patientstreated with radical intent for non-metastatic MIBC from 1999 to 2021 (either RC or TMT). All studies included specifically reported QoL for one of the main treatment approaches explored (RC followed by ileal conduit urinary diversion-ICUD, ONB or TMT). Pooled analysis for EORTC QLQ-C30 and BLM-30 questionnaires showed that ONB yielded a significant advantage only for Physical Functioning (pooled mean standardized difference -0.73 SD, p-value 0.019, I 2 = 93 %) and for Emotional Functioning (pooled mean standardized difference -0.16 SD, p-value 0.029, I 2 = 0 %). A trend in favour of higher mean reported values after TMT for Global Health Score, Physical Functioning and Role Functioning was found, if compared to both RC approaches. Significant benefit for ONB if compared to ICUD was detected only for specific subdomains of QoL questionnaires. No direct comparison with TMT is available, but data suggest advantage of this approach when compared to both reconstructive scenarios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest IM received a small fee for occasional attendance at the advisory board supported by Lilly, Novartis, Pfizer, Seagen, Accuray which is not related to the contents of this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Postoperative radiation therapy after breast conserving surgery in the older adult population is a matter of debate; although radiation therapy was shown to benefit these patients concerning local disease control, the absolute benefit was small and potentially negligible. Partial breast irradiation has been introduced as an alternative treatment approach for low-risk patients. Older adult patients with early breast cancer constitute a unique population with regards to prognosis and potential comorbidities, thus minimizing treatment to maintain health-related quality of life (HRQoL) without compromising survival is extremely important. Estimates of the patient's risk of benefit and/or harm with treatment should be performed together with an assessment of baseline comorbidities, life expectancy, and care preferences. Published data suggest that radiation therapy or endocrine therapy alone resulted in excellent disease control in older women with early breast cancer, and that the combination of both treatments has less incremental benefit than expected. Conversely, the toxicity profile of endocrine therapy is well known, often significantly impacting long term HRQoL of these potentially frail patients., Methods: Patients older than 70  years receiving breast conserving surgery with T1N0, Luminal A-like tumors will be randomized to receive partial breast irradiation-alone or endocrine therapy-alone. The main objectives are to determine patient reported outcome measures in terms of HRQoL, as assessed by the EORTC QLQ-C30 using the global health status of patients, and to demonstrate a non-inferior local control rate between arms. Secondary endpoints are represented by individual scales from QLQ-C30 and module QLQ-BR45 scores; ELD14 questionnaire; geriatric COre DatasEt assessment; distant control rate, adverse events rates, breast cancer specific, and overall survival., Discussion: The EUROPA trial is a new randomized trial focused on older adults (≥70  years) affected by good prognosis primary breast cancer. Our assumption is that postoperative radiation therapy-alone avoids the long-term toxicity of endocrine therapy and favorably impacts on HRQoL in this population. In the current report we present the trial's background and methods, focusing on perspectives in the field of precision medicine., Trial Registration: The trial is registered with ClinicalTrial.gov Identifier NCT04134598 / EUROPA trial., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Orbital lesions are rare, but are likely to become symptomatic and can impact on patients' quality of life. Local control is often difficult to obtain, because of proximity to critical structures. CyberKnife stereotactic robotic radiotherapy could represent a viable treatment option., Materials and Methods: Data on patients treated for intraorbital lesions from solid malignancies were retrospectively collected. All patients underwent treatment with CyberKnife system. We analyzed local control, response rate, symptoms control, progression-free survival and overall survival, acute and late toxicity., Results: From January 2012 to May 2017, 20 treatments on 19 patients were performed, with dose ranging from 24 to 35 Gy in 1 to 5 fractions, prescribed at an average isodose line of 79.5% (range: 78-81). After a mean follow-up of 14.26 months (range: 0-58), overall response rate was 75%, with 2 and 4 patients presenting a partial and complete response, respectively. Mean time to best measured response was 15.16 months (range: 2-58). Thirteen patients were alive, with a local control rate of 79%. Mean time to local progression was 5 months (range: 3-7). Three patients reported improvement in symptoms after treatment. Mean planning target volume dose coverage was 97.2% (range: 93.5-99.7). Mean maximum dose (D max) to eye globe, optic nerve, optic chiasm, and lens was 2380.8 cGy (range: 290-3921), 1982.82 cGy (range: 777.3-2897.8), 713.14 cGy (range: 219.5-2273), and 867.9 cGy (range: 38-3118.5). Four patients presented acute toxicity., Conclusion: This current retrospective series demonstrated that CyberKnife robotic stereotactic radiotherapy is a feasible and tolerable approach for intraorbital lesions.