Search Results (42)

Background: Ultra-hypofractionated whole-breast irradiation (WBI) delivering 26 Gy in five fractions has been established as a standard of care following the FAST-Forward trial. However, real-world data addressing advanced delivery techniques and the feasibility of incorporating a simultaneous integrated boost (SIB) remain limited. Methods: We retrospectively analyzed 40 patients with early-stage breast cancer (pT1–2N0M0) treated with breast-conserving surgery, followed by ultra-hypofractionated WBI using helical tomotherapy. Patients received either WBI alone (26 Gy in five fractions) or WBI with an SIB to the tumor bed (29–30 Gy in five fractions). Dosimetric parameters for planning target volumes (PTVs) and organs at risk (OARs) were evaluated. Acute skin toxicity was assessed using CTCAE version 5.0. Results: The median patient age was 55.7 years. The mean PTV V95% was 97.8%, with excellent hotspot control (PTV V105% < 5% and V107% < 2%). For left-sided tumors, the mean heart dose was 1.67 Gy, and the ipsilateral lung V8Gy remained below 15% in all patients. Acute radiation dermatitis was limited to Grade 0–1 in all cases. At a median follow-up of 14.8 months, both local control and overall survival were 100%. Conclusions: Ultra-hypofractionated WBI delivered using helical tomotherapy, with or without SIB, demonstrates robust dosimetric quality, minimal acute toxicity, and favorable early clinical outcomes in routine clinical practice. Full article

Objective: This study aims to report the early safety outcomes from an ongoing single-center, non-randomized phase 2 trial on focal salvage stereotactic radiotherapy (s-SBRT) for local prostate cancer recurrence. Materials and methods: This prospective phase 2 study includes patients with local recurrence after conventional or hypofractionated radiotherapy, ultrahypofractionated radiotherapy, or post-prostatectomy radiotherapy. The present analysis includes an initial subset of 21 out of 55 planned patients. All patients undergo mpMRI and PSMA-PET; biopsy is not required if imaging results are unambiguous. Focal s-SBRT is delivered to the recurrent lesion with a dose of 5 × 6.75 Gy. The primary endpoint is the rate of treatment-related CTCAE v5.0 grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicity. Secondary endpoints include early biochemical response (BR), defined as any PSA decline at 3 months. Results: With a median follow-up of 14 months (range: 4.5–25), one patient (4.8%) experienced both early and persistent late Grade 3 GU toxicity (bladder bleeding). Late Grade 2 GU and GI toxicities occurred in five (23.8%) and one (4.8%) patients, respectively. In exploratory univariable analysis, PTV volume 13 cc was identified as a marginal predictor for increased GU/GI radiation reactions (p < 0.1). Regarding efficacy, all 21 patients (100%) demonstrated an early biochemical response, with 15 patients (71.4%) achieving a PSA reduction of 50%. Conclusions: Focal s-SBRT demonstrates a favorable early safety profile and consistent biochemical response, supporting the preliminary safety of this ongoing study. Full article

Background/Objectives: Radiotherapy de-escalation is an established strategy in the management of early breast cancer, supported by randomized evidence predominantly derived from older patient populations. Younger women remain underrepresented in de-escalation trials, despite exhibiting less favorable clinicopathological characteristics associated with increased locoregional recurrence and inferior survival. The objective of this systematic review is to assess the available evidence regarding the safety and implementation of radiotherapy de-escalation strategies in younger patients with early breast cancer. Methods: A literature search following the PRISMA 2020 guidelines was performed to identify studies evaluating radiotherapy de-escalation strategies in younger breast cancer patients. Ongoing and recently completed trials were identified through ClinicalTrials.gov. Epidemiological data, randomized trials, and current clinical guidelines were reviewed. Results: Younger age at diagnosis is consistently associated with more aggressive tumor biology, higher rates of nodal involvement, unfavorable molecular subtypes, and worse survival outcomes. Among de-escalation approaches, moderate hypofractionation (15–16 fractions) is supported by randomized evidence and contemporary guidelines and can be applied irrespective of age. In contrast, evidence supporting ultra-hypofractionation, partial breast irradiation, and omission of radiotherapy in younger patients remains less robust, as these strategies have largely been evaluated in older or postmenopausal populations. Conclusions: Radiotherapy de-escalation in younger patients with breast cancer should be approached with caution. While moderate hypofractionation appears safe regardless of age, more aggressive de-escalation strategies lack adequate evidence in women under 50 years, particularly those under 40. Further prospective studies with sufficient representation of younger patients are required to clarify the role of radiotherapy de-escalation in this population. Full article

The 2025 Canadian Breast Cancer Symposium (CBCS) brought together patients, clinicians and researchers from across Canada to discuss advances shaping personalized breast cancer care. Key updates in systemic therapy highlighted expanding treatment options, including CDK4/6 inhibitors, oral SERDs, PI3K/AKT-targeted therapies, and antibody–drug conjugates across early and metastatic settings. Radiation oncology sessions emphasized treatment de-escalation, featuring evidence for ultra-hypofractionation, selective omission of nodal irradiation, and stereotactic strategies to manage oligoprogression. Surgical presentations focused on reducing morbidity through tailored axillary management and emerging techniques to prevent lymphedema. Advances in the management of central nervous system metastases underscored the growing synergy between stereotactic radiotherapy and CNS-active systemic therapies. Informed by patient testimony and advocacy perspectives, experts reflected on persistent gaps in diagnosis, access, and survivorship that shape priorities for future improvements. Together, these insights outline key directions that help to refine clinical practice and guide future research. Full article

Purpose/Objective(s): Adjuvant radiation therapy (RT) is an effective treatment in the management of patients with breast cancer. Evidence supports both standard fractionation and, more recently, moderate hypofractionation and ultra hypofractionation leading to a potential diversity of clinical practice. Whether or not physicians at main academic centers adopt hypofractionated regimens more readily than those working at community centers is not known. Practice patterns were analyzed within our large healthcare network comprising one main and eight community sites before and after 2020. Materials/Methods: Patients treated with adjuvant breast RT between 2017 and 2022 in our radiation oncology department were identified. Treatment techniques were evaluated: standard fractionation (25–28 fractions to 50–50.4 Gy), moderate hypofractionation (15–16 fractions to 40.05–42.56 Gy), and ultra hypofractionation (5 fractions of 26–30 Gy) for intact breast, partial breast, and chest wall cases. Use of each technique was compared between the main academic center (Main) versus eight community sites (Community) in two time periods, 2017–2019 and 2020–2022. Differences were assessed using z-ratios for the difference between independent proportions. Results: There was a statistically significant decrease in the use of standard fractionation for intact breast and chest wall cases from the early to the late period at both the community sites and the main center; however, a higher proportion of patients were treated with standard fractionation at the community sites versus the main center in the late period (7.8% community versus 2.0% main, p < 0.01 for intact breast and 80.7% community versus 37.4% main, p < 0.01 for chest wall). There was a statistically significant increase in the use of hypofractionation for intact breast and chest wall cases from the early to the late period at both the community sites and the main center; however, a higher proportion of patients were treated with hypofractionation at the main center versus the community sites during the late period (92.2% community versus 98.0% main, p < 0.01 for intact breast and 19.3% community versus 62.6% main, p < 0.01). Conclusions: The present study shows that recent trial evidence supporting the use of shorter RT treatments changed practice among providers more rapidly at our main academic center versus our community sites. The reasons for this difference are not known; however, standardization of treatment by implementation of an adjuvant RT treatment algorithm may facilitate uniform care among patients with breast cancer and we are investigating the impact of this approach. Full article

Background and Objectives: Ultra-hypofractionated radiotherapy (uhRT) is increasingly used for low- and intermediate-risk localized prostate cancer, necessitating exceptional precision compared to conventional fractionation. CBCT-based online-adaptive uhRT may help mitigate pelvic organ motion but has not yet been established in clinical routine. We report initial clinical experiences focusing on the feasibility and technical aspects of treatment delivery. Materials and Methods: Seven patients (35 fractions) with low- or intermediate-risk prostate cancer were treated with online-adaptive uhRT on the Varian Ethos^® system within routine clinical care. The target included the prostate and proximal seminal vesicles (CTV1, 5 × 7.25 Gy), with an integrated boost to the prostate (CTV2, 5 × 8.00 Gy). For each fraction, dose–volume histogram (DVH) parameters for targets and organs at risk (OARs) were recorded retrospectively for both scheduled and adaptive plans, along with the plan selection decision. Plan quality was evaluated per clinical DVH constraints and target coverage. The treatment time was recorded. Results: Online-adaptive uhRT was successfully delivered every day in 5 patients and on alternate days in 2 patients. Mean treatment time was 30:17 (±05:49 SD) minutes per fraction. The median recorded change in target and OAR volumes was <10%. Adaptive plans resulted in a statistically significantly improved target coverage for CTV1 (V100%, p = 0.01), PTV1 (D98%, p < 0.001), PTV2 boost (D98%, p < 0.001) in Wilcoxon signed-rank tests. OAR dose reduction was limited, with a small improvement in bladder V40Gy (p = 0.02). Adaptive plans were applied in 32/35 fractions (91.4%). To encompass intra-fractional motion in 95% of fractions, positional adjustments up to 0.77 cm (longitudinal), 0.37 cm (lateral), and 0.59 cm (sagittal) were required. Conclusions: Online-adaptive uhRT appears feasible, leading to optimized target volume coverage. Considerable treatment times must be taken into account. A second CBCT is recommended to compensate for intra-fractional motion. Further research regarding patient-related endpoints and cost-effectiveness is highly needed. Full article

To explore a more personalized approach to radiation therapy for adjuvant whole-breast irradiation in triple-negative breast cancer (TNBC), we analyzed the cell lines BT549 and MDA-MB-231 as in vitro models for radiobiological characterization. The local disease-free survival (LSR) values were determined for both cell lines’ median, maximum, and minimum α and β parameters to achieve an LSR probability of close to 100% in a five-fraction schedule. Based on these findings, fifteen treatment plans were created for BC to simulate the proposed dose schedule. For the MDA-MB-231 cell line, the α/β ratios were 3.79 Gy (minimum), 15 Gy (maximum), and 7 Gy (median). For the BT-549 cell line, the α/β ratios were 5.95 Gy (minimum), 22.93 Gy (maximum), and 16.51 Gy (median). To achieve an LSR probability of close to 100%, the required doses per fraction were 5.2 Gy, 5.3 Gy, and 7.3 Gy for MDA-MB-231 and 8 Gy, 9.1 Gy, and 9.9 Gy for BT-549. We selected the highest dose per fraction, 9.9 Gy × 5, to simulate the worst-case scenario. To achieve 100% cell death effectiveness in TNBC, it is likely that higher radiation doses are required—doses that are not feasible within the setting of adjuvant whole-breast irradiation. Our model, which relies on the intrinsic biological features of the tumor, paves the way to reach more tailored RT plans and to improve the classic LQ model. Full article

Advancements in radiotherapy (RT) techniques such as intensity modulation, image guidance, and hypofractionation have facilitated a satisfactory survival outcome in prostate cancer (PCa) patients. However, virtually all PCa patients suffer from various types and extents of radiation toxicities, which are mainly gastrointestinal (GI) and genitourinary (GU) in nature, eroding their quality of life. Thus, early mitigation and preventative measures should be offered, enabled by accurate toxicity prediction. This scoping review provides a comprehensive summary of reported acute and late GI and GU toxicity predictors of conventional fractionation (CFRT), moderate hypofractionation (MHRT), and ultra-hypofractionation (UHRT). A total of 169 studies published between the years 2000 and 2024 (inclusive) were identified from four databases, with 127 and 78 studies investigating GI and GU toxicities, respectively. Univariate analysis was employed in 139 studies to identify predictors, while 94 studies involved multivariate analysis, 40 involved internal model validation, and 5 performed external model validation. Among all studies, dosimetric predictors are the most reported factors, followed by patient, clinical, treatment, disease, genetic, and radiomic features. However, their applicability and performance have not yet been extensively proven in external validation involving multicenter studies. Future predictive studies should also focus on deeper multimodality information, such as radiomics, in addition to the categories of factors consolidated in this study, for an all-rounded investigation. A multicenter study is highly encouraged for prospective external validation. Further investigations into delivered doses and sub-volumes of various regions of interest are necessary. Comprehensive reporting items suggested in this work shall facilitate the reproducibility and comparability of the results. Full article

Background/Objectives: The SU2C-SARC032 randomized controlled trial (RCT) tested pembrolizumab combined with preoperative normofractionated radiotherapy as an intensified treatment for high-risk stage III resectable soft tissue sarcoma (STS), demonstrating a moderate improvement in disease-free survival (DFS) compared to preoperative radiotherapy alone, but accompanied by significantly increased toxicity, prolonged treatment durations, elevated resource source, and limited real-world applicability. To address the gap between highly controlled trial outcomes and routine clinical practice, this comparative analysis evaluated a streamlined ultra-hypofractionated preoperative radiotherapy (uhpRT) protocol using real-world data (RWD) as a potentially more balanced approach. Methods: Prospectively collected observational RWD from 54 consecutive patients with Stage III (T2 N0 M0) high-risk resectable STS treated at a single institution with uhpRT (25 Gy in 5 fractions in one week, no systemic therapy, median interval of 14 days to surgery) were analyzed. Survival endpoints (overall survival [OS], DFS, local disease-free survival [LDFS], distant disease-free survival [DDFS]), toxicity, and treatment duration were compared qualitatively with published outcomes from the SU2C-SARC032 trial’s intensified pembrolizumab arm and control arm. Results: At 2 years, the optimized uhpRT protocol achieved OS (90%), DFS (66%), and DDFS (70%) comparable to the intensified pembrolizumab arm (OS: 88%, DFS: 67%, DDFS (67%)) and clearly exceeded outcomes of the control arm (OS/DFS/DDFS: 85%/52%/52%). Importantly, the uhpRT protocol markedly reduced treatment-related toxicities (0% Grade 3/4 events vs. 56% in the intensified trial arm) and total treatment duration (<1 month vs. 3–11 months). Conclusions: These findings challenge the necessity of broad treatment intensification for high-risk localized STS, strongly supporting the concept of therapeutic optimization. Given substantial real-world variability in treatment practices and feasibility highlighted by recent research, our findings advocate for treatment strategies that prioritize realistic applicability, patient safety, and value-based care principles over pure intensification. Full article

Background/Objectives: Over the past decade, significant advances have been made in image-guided radiotherapy (RT) particularly with the introduction of magnetic resonance (MR)-guided radiotherapy (MRgRT). However, the optimal clinical applications of MRgRT are still evolving. The intent of this analysis was to describe our institutional MRgRT utilization patterns and evolution therein, specifically as an early adopter within a center endowed with multiple other technology platforms. Materials/Methods: We retrospectively evaluated patterns of MRgRT utilization for patients treated with a 0.35-Tesla MR-Linac at our institution from April 2018 to April 2024. We analyzed changes in utilization across six annualized periods: Period 1 (April 2018–April 2019) through Period 6 (April 2023–April 2024). We defined ultra-hypofractionation (UHfx) as 5 or fewer fractions with a minimum fractional dose of 5 Gy. Electronic health records were reviewed, and data were extracted related to patient, tumor, and treatment characteristics. Results: A total of 823 treatment courses were delivered to 712 patients treated for 854 lesions. The most commonly treated sites were the pancreas (242 [29.4%]), thorax (172; 20.9%), abdominopelvic lymph nodes (107; 13.0%), liver (72; 8.7%), and adrenal glands (68; 8.3%). The median total prescribed dose of 50 Gy in five fractions (fxs) was typically delivered in consecutive days with automatic beam gating in inspiration breath hold. The median biologically effective dose (α/β = 10, BED10) was 94.4 Gy with nearly half (404, 49.1%) of all courses at a prescribed BED10 ≥ 100 Gy, which is widely regarded as a highly effective ablative dose. Courses in Period 6 vs. Period 1 more often had a prescribed BED10 ≥ 100 Gy (60.2% vs. 41.6%; p = 0.004). Of the 6036 total delivered fxs, nearly half (2643, 43.8%) required at least one fx of on-table adaptive radiotherapy (oART), most commonly for pancreatic tumors (1081, 17.9%). UHfx was used in over three quarters of all courses (630, 76.5%) with 472 (57.4%) of these requiring oART for at least one fraction. The relative utilization of oART increased significantly from Period 1 to Period 6 (37.6% to 85.0%; p < 0.001); a similar increase in the use of UHfx (66.3% to 89.5%; p < 0.001) was also observed. The median total in-room time for oART decreased from 81 min in Period 1 to 45 min in Period 6, while for non-oART, it remained stable around 40 min across all periods. Conclusions: Our institution implemented MRgRT with a priority for targeting mobile extracranial tumors in challenging anatomic locations that are frequently treated with dose escalation, require enhanced soft-tissue visualization, and could benefit from an ablative radiotherapy approach. Over the period under evaluation, the use of high-dose ablative doses (BED10 ≥ 100 Gy), oART and UHfx (including single-fraction ablation) increased significantly, underscoring both a swift learning curve and ability to optimize processes to maximize throughput and efficiency. Full article

Background/Objectives: The historically most commonly used preoperative radiotherapy regimen for soft tissue sarcomas (STSs) consists of 50 Gray (Gy) delivered in 25 fractions over 5 weeks, achieving excellent local control, but with significant challenges due to prolonged treatment duration and early side effects. Reducing therapy duration while maintaining optimal local and distant control would be highly beneficial for patients. We aimed to investigate the outcome of an ultrahypofractionated radiotherapy (uhRT) regimen which may represent a shorter and more patient-friendly alternative. Methods: This multi-center, open-label, phase 2 clinical trial with a clustered cohort design was conducted within the Swiss Sarcoma Network (SSN). Adult patients (aged ≥ 18 years) with STS of the extremities or superficial trunk and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–3 were included. Participants were assigned to either normofractionated radiotherapy (nRT) at 50 Gy in 25 fractions or uhRT at 25 Gy in 5 fractions. Data were collected prospectively in real-world-time clinical settings. The primary outcome was local recurrence-free survival (LRFS), with overall survival (OS) and wound complications as secondary outcomes. Results: Between March 2020 and October 2023, 138 patients were included in the study; 74 received nRT and 64 received uhRT. The median follow-up times were 2.2 years for uhRT and 3.6 years for nRT. The LRFS rates at 1 year were 97.0% for nRT and 94.8% for uhRT (p = 0.57). The two-year LRFS rates were 91.9% and 94.8%, respectively (p = 0.57). The one- and two-year OS rates were 97.1%/86.3% and 98.2%/88.8%, respectively (p = 0.72). The wound complication rate was comparable between the nRT (12.0%) and uhRT (12.5%) groups (p = 0.99). Conclusions: UhRT for STSs offers an effective and safe alternative to traditional nRT, with comparable early LRFS, OS and wound complication rates. Given the two-year median follow-up, which is critical for evaluating local recurrence, uhRT shows promise as a shorter and more convenient treatment regimen. UhRT may be a safe and effective alternative treatment option to traditional nRT. Full article

A 98-year-old patient with cognitive impairment and a history of squamous cell carcinoma of the nasal pyramid was referred to the radiation oncology department of our institution’s hospital given that surgery was not recommended. The lesion was sized 6 × 6 cm, ulcerated, and bleeding; was significantly impairing the patient’s health-related quality of life, causing pain; and was not responsive to analgesics, including opioids. The patient experienced deterioration of her general conditions, with a Karnofsky performance status of 40. A single radiotherapy (RT) fraction was delivered on a weekly basis for 3 weeks, up to a total dose of 21 Gy, using a VMAT technique (7 Gy/fraction). The patient was given three fractions of radiotherapy, during which she received continuous assistance due to episodes of mental disorientation and an altered sense of consciousness. One month after the conclusion of the treatment, the patient exhibited a nearly complete clinical response, with full pain relief and an improved health-related quality of life. This favourable clinical outcome was maintained for a period of four months following the conclusion of RT. A brief review was performed on the role of hypofractionated radiation therapy in elderly patients with locally advanced skin cancer of the head and neck region. Full article

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques. Full article

Background: The current standard of local treatment for patients with localized breast cancer (BC) includes whole breast irradiation (WBI) after breast-conserving surgery (BCS). Ultrahypofractionated WBI schemes (1-week treatment) were shown not to be inferior to the standard WBI. Tumor bed boost using photon intraoperative radiotherapy (IORT) is safe and feasible in combination with standard WBI. The aim of the present study is to assess, for the first time, the feasibility and safety of combining photon IORT with ultrahypofractionated WBI. Methods: Patients diagnosed with low-risk early BC candidates for BCS were included in this prospective study. IORT was administered at a dose of 20 Gy to the surface’s applicator, and WBI was administered 3–5 weeks after surgery at a total dose of 26 Gy in five consecutive days. Results: From July 2020 to December 2022, seventy-two patients diagnosed with low-risk early BC and treated in our institution were included in this prospective study. All patients completed the proposed treatment, and no severe acute or late grade 3 toxicity was observed 3 and 12 months after WBI, respectively. Conclusions: Our results confirm for the first time that the combination of ultrafractionation WBI and photon-IORT after BCS is a feasible and safe option in patients with early BC. Full article

Magnetic resonance imaging (MRI) provides excellent visualization of central nervous system (CNS) tumors due to its superior soft tissue contrast. Magnetic resonance-guided radiotherapy (MRgRT) has historically been limited to use in the initial treatment planning stage due to cost and feasibility. MRI-guided linear accelerators (MRLs) allow clinicians to visualize tumors and organs at risk (OARs) directly before and during treatment, a process known as online MRgRT. This novel system permits adaptive treatment planning based on anatomical changes to ensure accurate dose delivery to the tumor while minimizing unnecessary toxicity to healthy tissue. These advancements are critical to treatment adaptation in the brain and spinal cord, where both preliminary MRI and daily CT guidance have typically had limited benefit. In this narrative review, we investigate the application of online MRgRT in the treatment of various CNS malignancies and any relevant ongoing clinical trials. Imaging of glioblastoma patients has shown significant changes in the gross tumor volume over a standard course of chemoradiotherapy. The use of adaptive online MRgRT in these patients demonstrated reduced target volumes with cavity shrinkage and a resulting reduction in radiation dose to uninvolved tissue. Dosimetric feasibility studies have shown MRL-guided stereotactic radiotherapy (SRT) for intracranial and spine tumors to have potential dosimetric advantages and reduced morbidity compared with conventional linear accelerators. Similarly, dosimetric feasibility studies have shown promise in hippocampal avoidance whole brain radiotherapy (HA-WBRT). Next, we explore the potential of MRL-based multiparametric MRI (mpMRI) and genomically informed radiotherapy to treat CNS disease with cutting-edge precision. Lastly, we explore the challenges of treating CNS malignancies and special limitations MRL systems face. Full article