Search Results (268)

The increasing prevalence of brain metastases in cancer patients due to longer life expectancy and improvements in neuroimaging highlights the need for effective local treatments. Despite advancements in systemic targeted therapies, their low blood–brain barrier (BBB) penetrance limits their intracranial efficacy. Stereotactic radiosurgery (SRS) has largely supplanted whole-brain radiation therapy (WBRT) for patients with up to 10 brain lesions due to superior neurocognitive outcomes and high local control. While single-fraction SRS provides low radiation toxicity with smaller lesions, high-volume metastases necessitate doses above tolerance limits to achieve comparable local control. As tumor volume increases, the number of tumor cells also increases, requiring higher doses of radiation than the maximum tolerated doses reported in the RTOG 9005 study to achieve tumor control. Hypo-fractionated SRS (HySRS) permits the delivery of high radiation doses over 2–5 fractions, thus mitigating the risk of radiation toxicity while maintaining high local control. This review presents the available evidence and ongoing clinical trials on HySRS for the management of brain metastases. 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

Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT), guided by 2023 European Society for Radiotherapy and Oncology (ESTRO)-European Association of Neuro-Oncology (EANO) and 2025 American Society for Radiation Oncology (ASTRO) recommendations. The standard Stupp protocol (60 Gy/30 fractions with temozolomide [TMZ]) improves overall survival (OS) to 14.6 months, with greater benefits in O6-methylguanine-DNA methyltransferase (MGMT)-methylated tumors (21.7 months). Tumor Treating Fields (TTFields) extend median overall survival (mOS) to 31.6 months in MGMT-methylated patients and 20.9 months overall in supratentorial GBM (EF-14 trial). However, 80–90% of recurrences occur within 2 cm of the irradiated field due to tumor infiltration and radioresistance driven by epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) mutations, cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions, tumor hypoxia, and tumor stem cells. Pseudoprogression, distinguished using Response Assessment in Neuro-Oncology (RANO) criteria and positron emission tomography (PET), complicates response evaluation. Targeted therapies (e.g., bevacizumab; PARP inhibitors) and immunotherapies (e.g., pembrolizumab; oncolytic viruses), alongside advanced imaging (multiparametric magnetic resonance imaging [MRI], amino acid PET), support personalized RT. Ongoing trials evaluating reirradiation, hypofractionation, stereotactic radiosurgery, neoadjuvant therapies, proton therapy (PT), boron neutron capture therapy (BNCT), and AI-driven planning aim to enhance efficacy for GBM IDH-wildtype, but phase III trials are needed to improve survival and quality of life. Full article

Background/Objectives: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy, or total neoadjuvant therapy (TNT), followed by total mesorectal excision (TME). If the neoadjuvant treatment results in a clinical complete response (cCR), non-operative management of LARC might be possible. It is hypothesized that cCR rates will increase with increasing radiotherapy doses. By using proton therapy, doses to organs at risk (OAR) may be decreased. In preparation for a clinical trial on dose-escalated proton therapy for LARC, the purpose of this study is to establish the feasibility of proton therapy for dose-escalated hypofractionated radiotherapy of LARC. Methods: Ten patients, having previously received short course radiotherapy (SCRT) for LARC, were included in this planning study. Two photon plans and two proton plans were created for each patient: one with a standard 5 × 5 Gy fractionation and one dose-escalated up to 5 × 7 Gy. Proton plans were robustly optimized. For all plans the integral dose (ID) was computed, and for the proton plans relative biological effectiveness (RBE) distributions were calculated. Feasibility was assessed in terms of target coverage and OAR doses. Results: All treatment plans satisfied target coverage criteria. Three of the photon and two of the proton dose-escalated plans exceeded recommended OAR objectives. Proton IDs were on average lower by a factor of 1.97 compared to photon IDs. Mean doses to OAR were, in general, lower for protons. All proton RBE values in the escalated target volumes were between 1.09 and 1.16. Conclusions: The proposed dose escalation was found to be feasible. Protons can reduce the integral dose and mean doses to OARs compared to photons in both the dose-escalated and non-escalated cases. Differences in RBE between escalated and standard fractionation were small. Full article

Background: Radiation dose escalation for locally advanced pancreatic cancer (LAPC) using stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) or computed tomography (CT)-guided moderately hypofractionated ablative radiation therapy (HART) can achieve favorable outcomes although have not previously been compared. Methods: We performed a multi-center retrospective analysis of SMART (50 Gy/5 fractions) vs. HART (75 Gy/25 fractions or 67.5 Gy/15 fractions with concurrent capecitabine) for LAPC. Gray’s test and Cox proportional regression analyses were performed to identify factors associated with local failure (LF) and overall survival (OS). Results: A total of 211 patients (SMART, n = 91; HART, n = 120) were evaluated, and none had surgery. Median follow-up after SMART and HART was 27.0 and 40.0 months, respectively (p < 0.0002). SMART achieved higher gross tumor volume (GTV) coverage and greater hotspots. Two-year LF after SMART and HART was 6.5% and 32.9% (p < 0.001), while two-year OS was 31.0% vs. 35.3% (p = 0.056), respectively. LF was associated with SMART vs. HART (HR 5.389, 95% CI: 1.298–21.975; p = 0.021) and induction mFOLFIRINOX vs. non-mFOLFIRINOX (HR 2.067, 95% CI 1.038–4.052; p = 0.047), while OS was associated with CA19-9 decrease > 40% (HR 0.725, 95% CI 0.515–0.996; p = 0.046) and GTV V120% (HR 1.022, 95% CI 1.006–1.037; p = 0.015). Acute grade > 3 toxicity was similar (3.3% vs. 5.8%; p = 0.390), while late grade > 3 toxicity was less common after SMART (2.2% vs. 9.2%; p = 0.037). Conclusions: Ablative SMART and HART both achieve favorable oncologic outcomes for LAPC with minimal toxicity. We did not observe an OS difference, although technical advantages of SMART might improve target coverage and reduce LF. Full article

Radiation-induced keratoconjunctivitis sicca (KCS) is a significant late complication in dogs receiving radiation therapy for intranasal tumors, particularly with hypofractionated intensity-modulated radiation therapy (IMRT). This retrospective case-control study was performed to identify anatomical and dosimetric risk factors for KCS in 15 canine patients treated with IMRT delivered in 4–6 weekly fractions of 8 Gy. Orbital structures were retrospectively contoured, and dose–volume metrics (D50) were calculated. Receiver operating characteristic (ROC) curve analysis and odds ratios were used to evaluate the associations between radiation dose and KCS development. Six dogs (33%) developed KCS within three months post-treatment. Statistically significant dose differences were observed between affected and unaffected eyes for the eyeball, cornea, and retina. ROC analyses identified dose thresholds predictive of KCS: 13.8 Gy (eyeball), 14.9 Gy (cornea), and 17.0 Gy (retina), with the retina showing the highest odds ratio (28.33). To ensure clinical relevance, KCS was diagnosed based on decreased tear production combined with corneal damage to ensure clinical relevance. This study proposes dose thresholds for ocular structures that may guide treatment planning and reduce the risk of KCS in canine patients undergoing IMRT. Further prospective studies are warranted to validate these thresholds and explore mitigation strategies for high-risk cases. Full article

Breast-conserving surgery followed by external beam Radiotherapy (RT) is a standard approach for early-stage Breast Cancer (BC). This retrospective study aims to determine the risk of RT-induced lung cancer for both standard and hypofractionated treatments. Fifty-eight Sicilian women treated at Humanitas Istituto Clinico Catanese (Misterbianco, Italy) between 2015 and 2021 with standard fractionated 3D-CRT (50 Gy in 2 Gy/fraction) were included. All treatment plans were designed using a hypofractionated schedule (42.56 Gy in 2.66 Gy/fraction). An Eclipse™ plug-in script was developed using the Eclipse Scripting Application Programming Interface (ESAPI) to extract patient and treatment data from the Treatment Planning System and compute Organ At Risk (OAR) volume, Organ Equivalent Dose (OED), Excess Absolute Risk (EAR), and Lifetime Attributable Risk (LAR) using the Schneider Mechanistic Model and reference data from regional populations, A-bomb survivors, and patients with Hodgkin’s Disease (HD). The OED distributions exhibited a statistically significant shift toward higher values in standard fractionated plans (p < 0.01, one-tailed paired Student’s t-test), leading to increased EAR and LAR. These results indicate that hypofractionated treatment may lower the risk of radiation-induced lung cancer. The feasibility of a priori risk estimation was evaluated by integrating the script into the TPS, allowing rapid comparison of SF and HF plans during planning. Full article

Background/Objectives: Proton therapy delivers highly conformal doses to the target area without producing an exit dose, minimizing cumulative doses to healthy liver tissue. This study aims to evaluate current practices, challenges, and variations in the implementation of proton stereotactic body radiation therapy (SBRT) and hypofractionated therapy for liver malignancies, with the goal of providing a technical assessment to promote broader adoption and support future clinical trials. Methods and Materials: An extensive survey was conducted by NRG Oncology across North American proton treatment centers to assess the current practices of proton liver SBRT and hypofractionated therapy. The survey focused on key aspects, including patient selection, prescription and normal tissue constraints, simulation and motion management, treatment planning, quality assurance (QA), treatment delivery, and the use of image-guided radiation therapy (IGRT). Results: This survey captures the current practice patterns and status of proton SBRT and hypofractionated therapy in liver cancer treatment.  Proton therapy is increasingly preferred for treating inoperable liver malignancies due to its ability to minimize healthy tissue exposure. However, the precision required for proton therapy presents challenges, particularly in managing uncertainties and target motion during high-dose fractions and short treatment courses. Survey findings revealed significant variability in clinical practices across centers, highlighting differences in motion management, dose fractionation schedules, and QA protocols. Conclusion: Proton SBRT and hypofractionated therapy offer significant potential for treating liver malignancies. A comprehensive approach involving precise patient selection, treatment planning, and QA is essential for ensuring safety and effectiveness. This survey provides valuable insights into current practices and challenges, offering a foundation for technical recommendations to optimize the use of proton therapy and guide future clinical trials. Full article

BE following RT after breast-conserving surgery is a common concern, impacting patients’ quality of life. This study introduces a clinically meaningful classification system for BE and retrospectively evaluates its incidence among patients treated with normofractionated (nfRT) and hypofractionated (hfRT) regimens. Data from 1156 patients treated between 2011 and 2021 were analyzed. BE was graded according to the CTC and a so-called “WST classification” (grade 1: lymphatic drainage performed by the patient; grade 2: professional lymphatic drainage; grade 3: surgery). A total of 33%/17% developed BE according to the WST classification/CTC. Grade III BE was not reported. About 70% experienced a remission of BE during follow-up. Risk factors for the development of BE included RT of lymphatic drainage, complete axillary dissection compared to sentinel node dissection, and CTX. CTX was not confirmed in multivariate analysis. The incidence of BE did not differ significantly between the nfRT and hfRT groups, affirming the safety and comparability of hfRT regarding BE risk (HR: 0.833, p = 0.1219). This study emphasizes the importance of precise and standardized BE classification for improved treatment outcomes. Given its comparable risk profile and potential for enhanced therapy adherence, the findings support hfRT as a preferred regimen aligned with the current guidelines. Full article

Background: CDK4/6 inhibitor plus ET is a standard treatment for advanced HR+ BC. This study evaluates the efficacy and safety of CDK4/6 inhibitors with concurrent RT (SBRT and non-SBRT) in terms of pain, analgesic therapy changes, toxicities, and net clinical benefit (NCB). Methods: BC patients with bone metastases treated with RT and CDK4/6 inhibitor in the prospective observational COMBART study were analyzed. Pain was measured with the NRS. The NCB was defined by pain reduction (NRS), toxicity, and treatment changes. Adverse events (AEs) were graded per CTCAE v5.0. Statistical tests included chi-square and t-test. Results: Forty patients were treated with CDK4/6 inhibitor (palbociclib 30.8%, ribociclib 51.3%, abemaciclib 17.9%) and RT (131 lesions; 100 SBRT, 31 non-SBRT). The mean NRS score dropped from 3.52 (pre-treatment) to 1.31 (post-treatment) (p < 0.001), with better outcomes for patients treated with moderate hypofractionation (58.6% vs. 39.9% pain relief, p = 0.016). Pain relief was independent of the type of CDK4/6 inhibitor used (p = NS). Analgesic reduction was most common with palbociclib (35.4%, p = 0.001). Eight toxicities (grade 1–2) were reported. The NCB was 0.6 overall, higher with non-SBRT (0.74 vs. 0.52). Conclusions: RT plus CDK4/6 inhibitor, especially with moderate hypofractionation, significantly reduced pain with manageable toxicity. Analgesic therapy can often continue without stopping CDK4/6 inhibitor. Full article

Background: Combining external beam radiotherapy (EBRT) with high-dose-rate (HDR) brachytherapy (BT) enables biologically effective dose escalation in prostate cancer. However, comparative evaluation of such regimens using radiobiological modeling remains limited. Methods: Dose regimens based on clinical practice were analyzed using α/β values of 1.5 and 3 Gy for the prostate. Ten patients with available planning CT, pelvic MRI, and ultrasound-guided BT plans were retrospectively evaluated. Physical and biological dose distributions were recalculated for various EBRT and HDR-BT combinations. Biological effective dose (BED) values were determined for the prostate and organs at risk (OARs: anterior rectal wall, bladder base, urethra). Regimens yielding the highest ΔBED between prostate and OARs were considered most favorable. Results: All regimens met clinical dose constraints. The most favorable ΔBED profiles for bladder and rectum were observed with HDR-BT regimens (2 × 15 Gy) combined with either 23 × 2 Gy or 15 × 2.5 Gy EBRT, independent of the assumed α/β value. EBRT-only regimens achieved superior urethral sparing, while higher HDR doses led to increased urethral exposure. Conclusions: This study underscores the value of radiobiological modeling in differentiating and optimizing prostate cancer radiotherapy strategies. While the trade-offs between dose escalation and OAR sparing are clinically known, our biologically driven analysis provides a more quantitative foundation for selecting and tailoring combined EBRT/HDR-BT regimens in practice. Full article

Objective: The SHARON (Short course RadiatiON therapy for palliative treatment) Bone trial is a phase III randomized non-inferiority multicentric study comparing symptom relief for complicated bone metastases (BMs) achieved through hypofractionated accelerated palliative radiotherapy (RT) to a standard RT regimen. Methods: Eligible participants were adults with ECOG PS ≤ 3 who were referred for palliative RT for painful BMs. Patients were assigned to receive either 30 Gy delivered in 10 daily fractions or 20 Gy in 4 fractions over two consecutive days. The primary outcome was pain relief one month post-treatment. Pain relief and adverse events were also evaluated at 2, 3, 6, and 12 months after RT. This trial was registered at clinicaltrials.gov (NCT03503682). Results: Between February 2018 and November 2021, 83 patients were enrolled (30 Gy: 41; 20 Gy: 42). In the standard RT group, five patients did not complete the prescribed RT, while none in the experimental arm discontinued treatment (p = 0.026). Due to early mortality, the primary endpoint was evaluable in 73 patients (35 and 38 in the standard and experimental arms, respectively). The rate of complete pain response at one month was 22.9% and 28.9% in the 30 Gy and 20 Gy arms, respectively (p: 0.571). The overall pain response rates, which included complete and partial responses, were 74.3% and 78.9% in the 30 Gy and 20 Gy arms, respectively (p = 0.638), when considering at least a 2-point reduction in the numerical rating scale. In both arms, 4.8% of patients experienced Grade >2 toxicity. Conclusions: Administering 20 Gy in four fractions twice a day is non-inferior to the standard 30 Gy delivered in 10 fractions for pain relief in the context of complicated BMs. Furthermore, this regimen demonstrated comparable safety in terms of acute toxicity, with a lower incidence of definitive interruptions of radiotherapy. Full article

Background/Objectives: The management of localized prostate cancer with regional lymph node involvement (N1M0) presents significant clinical challenges. While once considered indicative of systemic disease, improved imaging and evolving treatment paradigms have redefined node-positive disease as potentially curable. This systematic review aims to assess current evidence regarding treatment modalities and outcomes for patients with localized N1M0 prostate cancer. Methods: A systematic review was conducted to identify studies evaluating therapeutic strategies for N1M0 prostate cancer. Eligible studies included randomized controlled trials, retrospective analyses, and consensus guidelines. Treatment approaches reviewed included radical prostatectomy (RP) with pelvic lymph node dissection (PLND), whole pelvic radiotherapy (WPRT), prostate-only radiotherapy (PORT), androgen deprivation therapy (ADT), and metastasis-directed therapy (MDT), including stereotactic body radiotherapy (SBRT). Key outcomes included overall survival (OS), biochemical recurrence-free survival (bRFS), disease-free survival (DFS), and treatment-related toxicity. Results: Multimodal approaches—particularly the combination of ADT with WPRT or adjuvant radiotherapy following RP—were associated with improved survival outcomes. Patients with limited nodal burden and undetectable postoperative prostate-specific antigen (PSA) levels derived the most benefit. The use of prostate-specific antigen membrane positron-emission tomography/computed tomography (PSMA PET/CT) enhanced detection and guided MDT in oligorecurrent disease. SBRT, simultaneous integrated boost (SIB), and hypofractionated regimens demonstrated promising efficacy with acceptable toxicity profiles. Conclusions: Node-positive localized prostate cancer is optimally managed with individualized, multidisciplinary strategies. Combining systemic and locoregional treatments improves outcomes in selected patients. Ongoing prospective studies are warranted to refine patient selection, optimize treatment sequencing, and integrate novel imaging and systemic agents. Full article

Purpose: To evaluate the long-term oncological outcomes and toxicity profile based on 24 years of follow-up in patients with localized very high-risk prostate cancer (VHR PCa) treated with a combination of high-dose-rate brachytherapy (HDR-BT) and pelvic external beam radiation therapy (EBRT). Methods: A retrospective analysis was conducted on 87 patients with VHR PCa, classified according to National Comprehensive Cancer Network (NCCN) criteria, who received HDR-BT and EBRT. Androgen deprivation therapy (ADT) was administered to 72 patients (82.8%). The primary endpoints were biochemical control and cancer-specific survival (CSS), while the secondary endpoints included local control rates, tumor-free survival (TFS), overall survival (OS), and treatment-related toxicity. Results: The 24-year biochemical control rate was 68% (standard deviation [SD]: ±4%), while CSS and TFS at 24 years were 82% (SD ±4%) and 78% (SD ±4%), respectively. Local control rates remained at 98% at 24 years. Furthermore, the OS rate at 24 years was 30%. Multivariate Cox regression analysis identified the T category in the TNM classification as the only factor significantly associated with biochemical control, with 24-year rates of 69%, 71%, and 50% for patients with T-classifications of ≤T2c, T3a, and T3b-T4, respectively (p = 0.024). Notably, no grade ≥3 late toxicities were observed during the follow-up period. Conclusions: The 24-year outcomes support the viability and therapeutic efficacy of EBRT combined with a conformal HDR-BT boost for patients with VHR PCa. 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