Search Results (42)

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

The global cancer burden, especially in low- and middle-income countries (LMICs), worsens existing disparities, amplified by the rising costs of advanced treatments. The shortage of radiation therapy (RT) services is a significant issue in LMICs. Extended conventional treatment regimens pose significant challenges, especially in resource-limited settings. Hypofractionated radiotherapy (HRT) and ultra-hypofractionated/stereotactic body radiation therapy (SBRT) offer promising alternatives by shortening treatment durations. This approach optimizes the utilization of radiotherapy machines, making them more effective in meeting the growing demand for cancer care. Adopting HRT/SBRT holds significant potential, especially in LMICs. This review provides the latest clinical evidence and guideline recommendations for the application of HRT/SBRT in the treatment of breast, prostate, and lung cancers. It emphasizes the critical importance of rigorous training, technology, stringent quality assurance, and safety protocols to ensure precise and secure treatments. Additionally, it addresses practical considerations for implementing these treatments in LMICs, highlighting the need for comprehensive support and collaboration to enhance patient access to advanced cancer care. Full article

Radiotherapy for ultracentral lung tumors represents a treatment challenge, considering the high rates of high-grade treatment-related toxicities with stereotactic body radiation therapy (SBRT) or hypofractionated schedules. Accelerated hypofractionated magnetic resonance-guided adaptive radiation therapy (MRgART) emerged as a potential game-changer for tumors in these challenging locations, in close proximity to central organs at risk, such as the trachea, proximal bronchial tree, and esophagus. In this series, 13 consecutive patients, predominantly male (n = 9), with a median age of 71 (range (R): 46–85), underwent 195 MRgART fractions (all 60 Gy in 15 fractions) to metastatic (n = 12) or primary ultra-central lung tumors (n = 1). The median gross tumor volumes (GTVs) and planning target volumes (PTVs) were 20.72 cc (R: 0.54–121.65 cc) and 61.53 cc (R: 3.87–211.81 cc), respectively. The median beam-on time per fraction was 14 min. Adapted treatment plans were generated for all fractions, and indications included GTV/PTV undercoverage, OARs exceeding tolerance doses, or both indications in 46%, 18%, and 36% of fractions, respectively. Eight patients received concurrent systemic therapies, including immunotherapy (four), chemotherapy (two), and targeted therapy (two). The crude in-field loco-regional control rate was 92.3%. No CTCAE grade 3+ toxicities were observed. Our results offer promising insights, suggesting that MRgART has the potential to mitigate toxicities, enhance treatment precision, and improve overall patient care in the context of ultracentral lung tumors. Full article

Radiotherapy (RT) has a fundamental role in the treatment of gynecologic malignancies, including cervical and uterine cancers. Hypofractionated RT has gained popularity in many cancer sites, boosted by technological advances in treatment delivery and image verification. Hypofractionated RT uptake was intensified during the COVID-19 pandemic and has the potential to improve universal access to radiotherapy worldwide, especially in low-resource settings. This review summarizes the rationale, the current challenges and investigation efforts, together with the recent developments associated with hypofractionated RT in gynecologic malignancies. A comprehensive search was undertaken using multiple databases and ongoing trial registries. In the definitive radiotherapy setting for cervical cancers, there are several ongoing clinical trials from Canada, Mexico, Iran, the Philippines and Thailand investigating the role of a moderate hypofractionated external beam RT regimen in the low-risk locally advanced population. Likewise, there are ongoing ultra and moderate hypofractionated RT trials in the uterine cancer setting. One Canadian prospective trial of stereotactic hypofractionated adjuvant RT for uterine cancer patients suggested a good tolerance to this treatment strategy in the acute setting, with a follow-up trial currently randomizing patients between conventional fractionation and the hypofractionated dose regimen delivered in the former trial. Although not yet ready for prime-time use, hypofractionated RT could be a potential solution to several challenges that limit access to and the utilization of radiotherapy for gynecologic cancer patients worldwide. 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

Large fractions of radiotherapy of 8 Gy (ultra-hypofractionated RT, ultra-hypoRT) promote anti-tumor immune responses that have been clinically substantiated in combination trials with immune checkpoint inhibitors (ICIs). In the current study, we postulated that ultra-hypoRT in combination with ICIs may enhance tumor clearance in NSCLC patients with locoregional relapse after radical chemo-RT. Between 2019 and 2021, eleven patients received re-irradiation with one or two fractions of 8 Gy concurrently with anti-PD1 immunotherapy (nivolumab or pembrolizumab). RT-related toxicities were negligible, while immune-related adverse events enforced immunotherapy interruption in 36% of patients. The overall response rate was 81.8%. Tumor reduction between 80 and 100% was noted in 63.5% of patients. Within a median follow-up of 22 months, the locoregional relapse-free rate was 54.5%, while the projected 2-year disease-specific overall survival was 62%. The results were independent of PD-L1 status. The current report provides encouraging evidence that a relatively low biological dose of RT delivered with 8 Gy fractions is feasible and can be safely combined with anti-PD-1 immunotherapy. Despite the low number of patients, the significant tumor regression achieved and the long-lasting locoregional control and overall progression-free intervals provide a basis to pursue immuno-RT trials with U-hypoRT schemes in this group of NSCLC patients of poor prognosis. Full article

Technological advances in MRI-guided radiation therapy (MRIgRT) have improved real-time visualization of the prostate and its surrounding structures over CT-guided radiation therapy. Seminal studies have demonstrated safe dose escalation achieved through ultrahypofractionation with MRIgRT due to planning target volume (PTV) margin reduction and treatment gating. On-table adaptation with MRI-based technologies can also incorporate real-time changes in target shape and volume and can reduce high doses of radiation to sensitive surrounding structures that may move into the treatment field. Ongoing clinical trials seek to refine ultrahypofractionated radiotherapy treatments for prostate cancer using MRIgRT. Though these studies have the potential to demonstrate improved biochemical control and reduced side effects, limitations concerning patient treatment times and operational workflows may preclude wide adoption of this technology outside of centers of excellence. In this review, we discuss the advantages and limitations of MRIgRT for prostate cancer, as well as clinical trials testing the efficacy and toxicity of ultrafractionation in patients with localized or post-prostatectomy recurrent prostate cancer. Full article

Background: We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. Methodology: In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7–19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0–85.7) years. The bDFS rates and late toxicity profile were evaluated. Results: Median treatment time was 10 (7–38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)—G2: 9.1%; G3: 0.5%; genitourinary (GU)—G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. Conclusion: Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity. Full article

Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V_40Gy/s) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications. Full article