Medical science monitor : international medical journal of experimental and clinical researchYajing Huang, Hao Wu
BACKGROUND The survival association of adjuvant radiotherapy (RT) in early-stage node-negative luminal (HR+/HER2-) breast cancer remains under evaluation, and whether this association is modified by tumor quadrant location is unknown. MATERIAL AND METHODS We identified 5831 patients with T1-2N0M0 luminal breast cancer treated with breast-conserving surgery from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2017), stratified by RT receipt. Breast cancer-specific survival (BCSS) was analyzed using Kaplan-Meier, Cox regression, and Fine-Gray competing-risk models, with a prespecified RT-by-quadrant interaction test. RESULTS RT was independently associated with a lower hazard of breast cancer-specific death (hazard ratio=0.623, 95% confidence interval: 0.512-0.792, P<0.001) in the Cox regression analysis. In the competing-risk Fine-Gray model, the subdistribution hazard ratio was 0.661 (95% confidence interval: 0.530-0.825, P<0.001). A significant interaction was observed between RT and tumor quadrant (P=0.019). Quadrant-stratified analyses showed a significant adjusted association between RT and a lower hazard of breast cancer-specific death for upper-inner and lower-outer quadrant tumors; estimates for upper-outer and lower-inner quadrant tumors were in the same direction but did not display statistical significance. Sensitivity analyses using the Fine-Gray model and E-value calculations were consistent with the primary findings. CONCLUSIONS In this observational study of T1-2N0M0 luminal breast cancer, a significant statistical interaction was observed between postoperative RT and tumor quadrant location, generating the hypothesis that the association between RT and BCSS varies according to primary tumor quadrant. These findings require prospective validation before informing individualized treatment decisions.
BMJ case reportsAlifya Altaf Lokhandwala, Jonathan Paly, Thomas Roberts, Jong Chul Park, Manisha Patel, Lori Wirth, Gilbert Youssef, Jennifer L Powers, Ross D Merkin
Lhermitte's sign (LS) is characterised by a brief electric shock-like sensation elicited by neck flexion that radiates down the spine and may extend into the posterior aspects of the legs. It is a clinical indicator of cervical or upper thoracic dorsal column dysfunction, most commonly due to demyelination or intrinsic spinal cord pathology. It may occur after head and neck (chemo)radiotherapy. We describe two patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma who developed LS following chemoradiotherapy. One patient developed protracted LS lasting 20 months beyond completion of definitive concurrent chemoradiotherapy with volumetric modulated arc radiotherapy and weekly cisplatin and another patient developed protracted LS after adjuvant de-escalated volumetric modulated arc radiotherapy lasting 12 months beyond treatment completion. These cases show the variable course of LS in the modern conformal era and highlight its benign prognosis but potential for persistent symptoms that affect patient quality of life.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in CancerDaniela Oliveira Vieira, Sérgio Barreira, Mário Dinis-Ribeiro, Eurico Monteiro
PURPOSE: Oropharyngeal dysphagia is a frequent long-term sequela in survivors of oropharyngeal cancer treated with chemoradiotherapy (CRT), with significant impact on quality of life (QoL). Flexible endoscopic evaluation of swallowing (FEES) provides objective information on swallowing physiology, whereas patient-reported outcome measures (PROMs) capture perceived dysphagia burden. This study explored how FEES findings and PROMs provide complementary information regarding dysphagia in disease-free survivors treated with CRT. METHODS: A cross-sectional study was conducted in 38 disease-free survivors of oropharyngeal cancer treated with CRT. Swallowing was assessed using FEES, including measures of swallowing safety, efficiency and temporal physiology. Swallowing-related QoL and symptom burden were assessed using the EORTC QLQ-C30, EORTC QLQ-H&N43, and SWAL-QOL questionnaires. Associations between objective and subjective outcomes were explored using correlation and comparative analyses. RESULTS: FEES identified frequent swallowing impairments, particularly pharyngeal residue, increased number of swallows for solid consistencies and penetration-aspiration events. PROMs also revealed substantial dysphagia-related burden, with the SWAL-QOL identifying the highest proportion of altered results. Associations between FEES findings and QoL domains were observed; however, no consistent one-to-one relationship between physiological impairment and patient-reported burden was identified. CONCLUSION: FEES and PROMs capture complementary dimensions of dysphagia in disease-free survivors of oropharyngeal cancer after CRT. FEES identifies physiological swallowing impairments, whereas PROMs reflect the functional and psychosocial impact of dysphagia. Combined use of instrumental and patient-reported assessments may improve supportive care and long-term follow-up in this population.
Journal of neuro-oncologyShashank Rajkumar, Harrison Moy, XueMei Ji, Mariam Aboian, Veronica Chiang
PURPOSE: Stereotactic radiosurgery (SRS) effectively treats brain metastases, yet some lesions ultimately require post-SRS surgery due to local failure. We examined whether the use of volumetric changes in FLAIR hyperintensity and/or necrosis in conjunction with enhancing volumetric changes after Gamma Knife SRS correlate with pathological outcome at subsequent surgery. METHODS: We queried our institutional database for patients who received first-time SRS for a single brain metastasis and later underwent surgical resection of the same lesion. Tumor volumes were measured manually before SRS and at 6 weeks, 3 months, and 6 months post-treatment. FLAIR:enhancing (FER) and enhancing:necrotic ratios were analyzed. Linear mixed-effects models assessed variables influencing volume trajectories; Pearson correlation examined associations with pathological outcome. RESULTS: Thirty-six patients met inclusion criteria. Mean enhancing volume changed - 28.5%, - 25.8%, and - 18.9% from baseline at 6 weeks, 3 months, and 6 months, respectively. Mean FLAIR volume changed - 16.9%, - 22.2%, and - 2.4% at the same intervals. Percent changes in FLAIR and enhancing volume correlated significantly at 6 weeks (p = 0.004) and 3 months (p < 0.001). FER trended differently between RN and recurrent tumor with patients who developed radiation necrosis (RN) having significantly lower FLAIR volumes at 6 weeks compared to those with recurrent tumor. Baseline lesion size, FLAIR volume, FER (all p < 0.001), primary cancer type, and sex (both p = 0.02) influenced FLAIR trajectories. CONCLUSIONS: Perilesional edema and enhancement trajectories after SRS are variable but may help distinguish RN from recurrent tumor, particularly at early follow-up. Incorporation of automated edema volumetry should be considered in routine post-SRS surveillance.
Radiation oncology (London, England)Dorothea H Kopp, Anna Chiara Giovannelli, Felix Mehrhof, Sebastian Zschaeck, Marcus Beck, Anna Dieper, Paul Krahl, Moritz V Scharr, Jacek Nadobny, Jens-Uwe Blo…
PURPOSE: Hyperthermia (HT) enhances the effects of radiotherapy (RT) and has shown benefit in recurrent breast cancer. Most existing studies focus on conventional superficial HT, whereas the efficacy of regional hyperthermia (RHT) and capacitive hyperthermia (CHT) in previously irradiated areas remains underexplored. METHODS: Patients with locoregional breast cancer recurrences previously treated with RT were included in this retrospective analysis. Re-irradiation was delivered in combination with RHT or CHT and was integrated into an individualized multimodal treatment concept. HT was applied once or twice weekly immediate following RT, with temperature monitoring performed for RHT. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and toxicity. RESULTS: A total of 15 patients with 17 locoregional recurrences were included. Patients received re-RT with a median dose of 50 Gy and a median of 7 HT sessions (range, 1-24 sessions; Interquartile range (IQR), 5.5-10). After a median follow-up of 30.1 months (range, 5-76 months; IQR, 13-43) two patients experienced local progression during follow-up. The estimated 2-year PFS was 75%, and OS was 60% at last follow-up. Acute and late toxicities were limited to grade 1-2 events, with no grade ≥ 3 toxicity observed. CONCLUSION: This retrospective analysis demonstrates the feasibility of combining RHT or CHT with multimodal treatment in patients with recurrent breast cancer and provides encouraging preliminary clinical outcomes. Despite the limitations, these findings support the integration of RHT and CHT into salvage treatment strategies and justify further prospective investigation. CLINICAL TRIAL NUMBER: Not applicable.
BMJ openSamuel Lichtman-Mikol, Joshua M Lang, Himanshu Nagar, Raed Zuhour, Kevin V Chaung, Nicholas G Zaorsky, Soumyajit Roy, Prateek M Mendiratta, Jonathan E Shoag, J…
INTRODUCTION: Prostate cancer (PCa) is the most commonly diagnosed cancer in men worldwide. A rising proportion of men present with de novo metastatic disease, a state associated with poor survival outcomes and limited curative treatment options. Within this group, a subset of patients exhibit oligometastatic disease, defined by a limited number of metastases, which may represent a distinct clinical entity with potential for long-term disease control. Emerging evidence suggests that metastasis-directed radiotherapy (MDRT), including stereotactic body radiation therapy (SBRT), may improve progression-free survival in this population. However, current evidence is largely limited to phase II trials in the metachronous setting and retrospective studies in the synchronous setting. Furthermore, predictive biomarkers of treatment response in these patients remain undefined. We aim to evaluate, within a large randomised multicentre phase II trial, the efficacy and biological impact of MDRT in men with de novo oligometastatic PCa. METHODS AND ANALYSIS: Patients with de novo oligometastatic hormone-sensitive prostate cancer (omHSPC), defined as up to 10 sites of metastatic disease by prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT or up to five sites of metastatic disease by conventional imaging, are randomised (1:1) to standard of care (SOC) or SOC plus MDRT. SOC includes 12 months of androgen deprivation therapy plus an androgen receptor pathway inhibitor, with definitive treatment to the prostate by radiotherapy (RT). A predefined subset is allowed to undergo radical prostatectomy if clinically appropriate. MDRT involves SBRT to all metastatic sites identified on conventional imaging or PSMA PET/CT. Target enrolment is 200 patients, stratified by diagnostic imaging modality, number of bone metastases, plan to MDRT all sites of metastases and local therapy approach.Prostate RT may be delivered using moderate (20 fractions) or ultra-hypofractionation (five fractions), with optional simultaneous-integrated-boost to dominant intraprostatic lesions. MDRT regimens aim for a biologically effective dose ≥100 Gy (α/β=1.5) using 1-5 fractions. Gross tumour volumes are delineated based on MRI, CT and PSMA PET/CT.The primary endpoint is failure-free survival, defined using cause-specific PCa death. The study is powered at 80% to detect a HR of 0.58 using a one-sided alpha of 0.05. Secondary endpoints include radiographic progression-free survival, overall survival (OS), time to next intervention, time to castration-resistant PCa, PCa-specific mortality and patient-reported outcomes. Biospecimen collection and imaging data will support future translational analyses. Data from this trial is preplanned to be pooled with the STAMPEDE 2 (NCT06320067) trial, a phase III randomised trial to assess OS benefit of MDRT in men with de novo omHSPC. ETHICS AND DISSEMINATION: This clinical trial is approved by the Case Comprehensive Cancer Center Institutional Review Board (STUDY20231440). The results will be disseminated via peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT06150417 (https://clinicaltrials.gov/study/NCT06150417).
PURPOSE: To evaluate dose selection and post-treatment management after Gamma Knife surgery (GKS) for large brain metastases, with a focus on early identification of true progression. METHODS: This retrospective single-institution study included 143 patients with large brain metastases (tumor volume ≥ 4 cm3) treated with primary GKS between 2016 and 2024. One dominant lesion per patient was analyzed. Treatment modality (single-session, staged, or hypofractionated) and dose selection were individualized. Radiographic progression was defined as a ≥ 20% increase in longest tumor diameter from nadir. True progression was defined as sustained enlargement or the need for salvage treatment, whereas lesions that stabilized or regressed without intervention were classified as pseudoprogression. RESULTS: Median overall survival was 15.3 months. During follow-up, 47 lesions showed radiographic progression: 42 true progression, 4 pseudoprogression, and 1 intratumoral hemorrhage. The 6-, 12-, and 24-month cumulative incidences of true progression were 17.4%, 31.5%, and 33.1%, respectively. True progression did not differ by treatment modality or tumor volume. A marginal dose ≥ 57.6 Gy biologically effective dose (BED10) was associated with a lower risk of true progression (subdistribution hazard ratio [SHR], 0.46; p = 0.02). Recurrent peritumoral edema developed earlier in true progression than pseudoprogression (median, 173.5 vs. 564 days; p = 0.001). Lower marginal dose at repeat GKS was associated with subsequent true progression (SHR, 0.82; p = 0.02). CONCLUSION: A BED10 ≥ 57.6 Gy improved local control in large brain metastases. Recurrent peritumoral edema accompanying tumor enlargement within 1 year after GKS strongly suggested true progression and should prompt consideration of early salvage intervention. CLINICAL TRIAL REGISTRATION: Clinical trial number: not applicable.
BACKGROUND: Evidence regarding repeated remimazolam administration remains limited. We hypothesized that remimazolam would be associated with fewer adverse events than propofol while maintaining stable sedative requirements across three repeated sedation sessions. METHODS: Patients with cervical cancer undergoing three fractions of interstitial brachytherapy were randomized to propofol or remimazolam. The primary outcome was the proportion of sedation episodes with at least one prespecified intraoperative adverse event across three sessions. Secondary outcomes included sedative dose, hemodynamics, and sleep quality assessed using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS). RESULTS: A total of 100 participants were randomized, of whom 91 completed all three prespecified sedation sessions and were included in the primary per-protocol analysis (46 in the propofol group and 45 in the remimazolam group). Across 138 propofol and 135 remimazolam episodes, overall adverse events were less frequent with remimazolam (17.78% vs. 59.42%; RR, 0.30; 95% CI, 0.18-0.49; p < 0.001). Respiratory depression (3.70% vs. 26.09%; RR, 0.14; 95% CI, 0.04-0.53; p = 0.004) and hypotension (8.15% vs. 41.30%; RR, 0.20; 95% CI, 0.09-0.42; p < 0.001) were also lower with remimazolam. Remimazolam requirements remained stable across sessions (third vs. first: mean difference, 0.19 mg; 95% CI, -0.78 to 1.15; p = 0.846). No significant between-group differences were observed in PSQI or AIS scores. CONCLUSION: Across three consecutive sedation sessions for interstitial brachytherapy, remimazolam was associated with fewer respiratory and hemodynamic adverse events than propofol, while sedative requirements remained stable across the three sessions. TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR2500108294).
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in CancerPhitjira Sanguanboonyaphong, Anyamanee Lapmag, Warisada Silaon, Praneet Opanasopit, Woraanong Thiramontre, Suphatcha Khiewvarn, Kanokporn Chamalerk, Worranan R…
BACKGROUND: Chemotherapy-associated oral mucositis (OM) is a prevalent and debilitating complication in patients undergoing cancer treatment, lacking effective preventive and therapeutic options. Boesenbergia rotunda (BR), a traditional medicinal plant, exhibits potent anti-inflammatory and antimicrobial activities. The objective of this study was to evaluate a BR extract-based mouth gargle for the management of concurrent chemoradiotherapy (CCRT)-induced OM. METHODS: BR extract was evaluated for cytotoxicity and anti-inflammatory activity. The mucoadhesive mouth gargle was characterized by antimicrobial activity, salivary release, and mucosal deposition. Clinical evaluation was performed in patients with head and neck cancer receiving CCRT in a prospective randomized controlled trial conducted between September 2024 and November 2025. The primary outcome of the clinical phase was to compare the incidence of OM at 6 weeks. RESULTS: BR extract was non-cytotoxic at concentrations below 1 µg/mL and significantly suppressed nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. The formulation demonstrated antimicrobial activity, rapid release within 2 min, and effective mucosal deposition. Fifty-six patients were enrolled, with 73.98% adherence. The incidence of overall OM was significantly lower in the BR extract group than in the control group (30.4% vs. 41.1%, p = 0.04). Lip swelling at week 3 occurred less frequently in the BR group than in the non-intervention group (1.8% vs. 14.3%, p = 0.03), while other adverse events were comparable between groups. CONCLUSION: The BR extract-based mucoadhesive mouth gargle is biocompatible, exhibits anti-inflammatory and antimicrobial activities, and achieves effective mucosal delivery. These findings indicate its potential as a therapeutic strategy for managing CCRT-induced OM. CLINICAL TRIAL NUMBER: Not applicable.
Bulletin of mathematical biologyFrancesco Albanese, Giulia Chiari, Marcello Edoardo Delitala
Tumor response to radiotherapy is strongly influenced by oxygen availability and phenotypic heterogeneity, yet their combined impact on the relative performance of fractionation schedules remains unclear. Here, we develop a mathematical model that integrates spatial oxygen dynamics with continuous phenotypic adaptation to hypoxia and radiation, and use it to systematically compare radiotherapy protocols under a common normal-tissue toxicity constraint. Under spatially uniform oxygenation, we find that alternative fractionation schedules provide little improvement over standard-of-care protocols in normoxic conditions. Under moderate hypoxia, however, a distinct class of protracted schedules with longer inter-fraction intervals substantially increases time-to-progression, in some cases by up to twofold. This regime-dependent benefit is consistent with a shift in the balance between reoxygenation and selection for resistant phenotypes. When oxygen delivery is spatially heterogeneous, treatment outcomes depend strongly on the geometric organization of oxygen sources. Even with identical total oxygen supply, different spatial configurations lead to large variability in time-to-progression and can alter the relative ranking of radiotherapy protocols. These results show that radiotherapy effectiveness is not an intrinsic property of a treatment schedule alone, but emerges from its interaction with tumor microenvironmental structure and evolutionary dynamics. Incorporating both spatial heterogeneity and phenotypic adaptation may therefore be important for the consistent evaluation and design of fractionation strategies in heterogeneous tumors.
MedicineZiyad S Almalki, Ahmad A Alamer, Shaheed K Alhumaid, Abdulrahman A Alsuhibani, Bandar S Alghamdi, Meshal M Alqahtani, Nawaf S Alzahrani, Osama A Alghamdi, Hait…
BACKGROUND: Adding pembrolizumab to standard concurrent chemoradiotherapy (CCRT) has shown substantial survival benefits in newly diagnosed, high-risk locally advanced cervical cancer (LACC), but its economic value in Saudi Arabia has not been established. This study assessed the cost-effectiveness of pembrolizumab plus CCRT versus placebo plus CCRT as first-line treatment for high-risk LACC from the perspective of the Saudi Arabian healthcare payer. METHODS: A partitioned survival analysis model was developed to project lifetime costs and quality-adjusted life-years (QALYs) for a hypothetical cohort of women with high-risk LACC in the Saudi public healthcare sector, using resource use patterns consistent with major tertiary care and specialized cancer centers. Clinical efficacy data were obtained from the KEYNOTE-A18 trial. Costs were sourced from official Saudi price lists, local hospital data, and a formal Structured Expert Elicitation process, and were reported in 2025 United States dollars. Health state utilities were derived from the literature. The primary outcome was the incremental cost-effectiveness ratio. Future costs and QALYs were discounted at an annual rate of 3%. Comprehensive deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: Adding pembrolizumab to CCRT resulted in an incremental gain of 3.51 life-years and 2.93 QALYs at an additional cost of $242,043 compared with placebo plus CCRT. At its current list price, the regimen yielded an incremental cost-effectiveness ratio of $82,626 per QALY. At a willingness-to-pay threshold of $90,000 per QALY, the probability of the pembrolizumab regimen being cost-effective was 67%. CONCLUSION: Pembrolizumab in combination with CCRT provides substantial clinical benefits in patients with high-risk LACC in Saudi Arabia. At the current price, this regimen is likely to be considered cost-effective. The analysis provides a strong, evidence-based rationale for significant price negotiations to ensure that the regimen delivers value to the Saudi healthcare system.
Journal of applied clinical medical physicsHaiyan Jiang, Zengtai Yuan, Zihao Liu, Yuxiang Wang, Wei Hu, Bing Yan, Yidong Yang
BACKGROUND: Radiation therapy treatment planning is a time-consuming trial-and-error process, and the plan quality is heavily dependent on planners' experiences, resulting in a strong demand for automated planning methods that can rapidly generate uniformly high-quality plans. PURPOSE: This study aimed to develop a hybrid automated deep learning-based plan optimization (HALO) framework, integrating deep learning fluence prediction and optimization, multileaf collimator (MLC) sequencing, and GPU-accelerated Monte Carlo dose computation. HALO was designed to ensure robust plan generation for cervical cancer intensity-modulated radiation therapy (IMRT). METHODS: The proposed HALO framework incorporated several functional modules. First, a dose-guided Fluence Prediction Network (DG-FPN) was developed. A total of 120 cervical cancer clinical IMRT plans were collected to train the DG-FPN, of which 90 plans were assigned for training, 10 for validation, and 20 for testing. The neural network took patients' computed tomography (CT) anatomy as input and predicted the 3D dose distribution and fluence maps. Next, the predicted fluence maps were further optimized to meet dose-volume constraints (DVCs), and then the refined fluence maps were converted into deliverable segments using an MLC sequencing algorithm. Finally, dose calculation was performed using a GPU-accelerated Monte Carlo engine. The 20 patients in the testing set were used to evaluate the HALO method, and the plan deliverability was validated by patient-specific IMRT Quality Assurance (QA). RESULTS: The DG-FPN achieved superior fluence prediction accuracy compared to previous work, with a median mean absolute error (MAE) of 0.055 and a structural similarity index (SSIM) of 0.94. The automated framework generated high-quality plans and reduced dose to adjacent OARs, with V50Gy decreased from 46.5 ± 5.0% to 41.5 ± 4.8% (p = 0.008)for bladder, V35Gy decreased from 31.5 ± 8.2% to 29.2 ± 7.5% (p = 0.024) for small intestine, while preserving PTV homogeneity and conformity. Importantly, the entire treatment planning time was within 3 minutes, with fluence optimization time decreased by an average of 82.6% after using deep learning prediction. The mean gamma passing rate under the 2%/2 mm criterion for the patient-specific IMRT QA achieved 97.37 ± 1.01%. CONCLUSIONS: This study demonstrated the clinical feasibility of the proposed HALO framework for cervical cancer radiotherapy in producing high-quality and deliverable IMRT plans. The proposed automated paradigm can serve as a stand-alone platform for treatment planning.
Journal of applied clinical medical physicsToshiro Tsubouchi, Noriaki Hamatani, Akira Komada, Masaaki Takashina
BACKGROUND: Log file-based patient specific quality assurance (PSQA) in scanned particle therapy relies on the consistency of spot position information recorded by the spot position monitor (SPM), but practical methods for routine independent verification of these coordinates remain limited. PURPOSE: This study describes a practical framework for routine verification of SPM coordinate consistency using independent scintillator-based measurements in raster-scanning carbon-ion radiotherapy. METHODS: Reference spot positions were measured at the isocenter plane using a scintillator-based detector. Corresponding SPM-recorded spot coordinates were extracted from delivery log files. The two coordinate sets were aligned using a similarity transformation accounting for translation, rotation, and isotropic scaling. Post-transformation root-mean-square (RMS) residuals were used as a practical consistency metric reflecting the agreement between SPM-reported and independently measured spot positions under routine QA conditions. RESULTS: After similarity transformation, the median RMS residual across all investigated accelerator energies and irradiation ports was 1.45 mm, with an interquartile range of 1.36-1.63 mm. No statistically significant difference was detected across accelerator energies, whereas a significant difference was observed among irradiation ports. CONCLUSIONS: The proposed framework provides a practical approach for routine verification of SPM coordinate consistency and for establishing facility-specific baselines through longitudinal monitoring. The RMS residual should not be interpreted as the intrinsic positional error of the SPM alone, but to provide a framework for establishing a facility-specific baseline for monitoring the agreement between SPM-reported and independently measured spot coordinates under routine QA conditions.
Journal of applied clinical medical physicsVictoria Bry, Angelia Tran, Tamara Egan, Eric Ford, Juergen Meyer
BACKGROUND: Surface Guided Radiation Therapy (SGRT) has become an increasingly important tool that complements x-ray imaging to improve patient safety for setup, respiratory tracking, and motion monitoring. As SGRT is integrated into clinical workflows, its complexity can introduce potential risk of process-related errors. These risks may depend on workflow design, system integration, equipment configuration, and technology specific features. As SGRT continues to expand across a wider range of treatment sites and clinical applications, comprehensive evaluation of institutional workflows is recommended to support safe and effective implementation. PURPOSE: This study aimed to identify and evaluate safety risks associated with the clinical use of SGRT using Failure Mode and Effects Analysis (FMEA). Emphasis was placed on workflow processes, system integration, and equipment-specific characteristics within a clinical environment to inform risk mitigation strategies and support safe implementation. METHODS: A multidisciplinary team performed an FMEA of SGRT related procedures and workflows. A process map was developed to define the scope of clinical applications, including tattoo free setup, free-breathing and deep-inspiration breath-hold (DIBH) breast treatments, prone patient positioning and real-time motion monitoring for stereotactic body radiation therapy (SBRT) patients across body sites. For each process step, team members identified potential failure modes associated with the clinical workflow and environment, including the integration of a C-RAD SGRT system with Elekta linear accelerators. Scoring was performed according to AAPM TG-100 guidelines, using severity (S), occurrence (O), and detectability (D) to calculate the Risk Priority Number (RPN). Failure modes were then ranked by RPN, and those with scores greater than or equal to 100 were selected for further analysis and development of mitigation strategies. RESULTS: Thirty-eight failure modes were identified, with nine having RPN scores greater than or equal to 100 (S = 5-8, O = 2-5, and D = 5-9). High risk failure modes were most associated with the DIBH workflow, particularly respiratory trace acquisition, respiratory trace configuration, and x-ray image verification. Additional high risk failure modes were identified in treatment preparation and system quality assurance processes, including manual data import, template selection, calibration, and daily QA procedures. These risks were primarily associated with workflow-dependent processes involving user interaction and coordination between integrated clinical systems. CONCLUSIONS: This FMEA identified workflow, system integration and equipment related vulnerabilities associated with SGRT implementation. The findings emphasize the importance of risk assessments tailored to specific clinical workflows and treatment environments and support the development of targeted mitigation strategies for safe clinical use.
Journal of applied clinical medical physicsShadab Momin, Eduard Schreibmann, Justin Roper, Beth Ghavidel, Maxine Washington, Oluwatosin Kayode, Pretesh Patel, Ashish Patel, Hania Al-Hallaq, Yulia Lyatsk…
BACKGROUND: Emergency palliative radiotherapy is often delivered under time-constrained and high-stress conditions, frequently bypassing conventional computed tomography (CT) simulation and relying on nonstandard workflows. These factors increase variability and the potential for error. PURPOSE: This work describes the development, implementation, and early clinical evaluation of a simulation-free, cone-beam CT (CBCT) based emergency radiotherapy workflow that leverages treatment planning system (TPS) scripting to standardize and automate deterministic steps while preserving clinical oversight. METHODS: An ESAPI scripting-driven emergency workflow was developed within the TPS to automate prescription handling, plan generation, beam configuration, dose calculation, and setup preparation using CBCT images. Safety checks were implemented in the form of prompts with the appropriate actions required. Alternatively, manual input was retained for image verification and treatment field borders definition. The workflow was implemented across multiple clinical sites within a single healthcare system and evaluated through dosimetric comparison of CT- and CBCT-based planning. Metric parameters such as workflow time, reductions in manual interactions, and pre- and post-training survey outcomes of automated 3D workflow were compared to the same parameters of the conventional 2D workflow. RESULTS: The automated workflow successfully generated clinically acceptable emergency treatment plans with minimal manual input. CBCT-based dose calculations demonstrated agreement with CT-based planning within 2.5% when heterogeneity corrections were enabled and within 4.7% when disabled. Automation eliminated 33 manual data entry steps present in the 2D workflow and enabled treatment delivery with average on-table time of approximately an hour. Survey results demonstrated strong staff support for automation, with over 90% anticipating improvement prior to training and 100% reporting perceived improvement following training. Staff comfort and confidence improved post-training, and concerns regarding workflow clarity and safety decreased. CONCLUSIONS: A scripting-based, simulation-free emergency radiotherapy workflow was developed for safe and standardized palliative treatments while maintaining established clinical safeguards. By automating deterministic planning tasks and preserving human oversight for clinical decision-making, the proposed approach improves consistency and staff confidence and has potential to improve safety and accuracy of palliative treatments.
Journal of applied clinical medical physicsFeng Lin, Jinyan Hu, Zhao Li, Jun Wang, Wenying Zhang, Aiping Wen, Mao Li, Yunfei Hu, Yang Wang
BACKGROUND: While computed tomography (CT) remains an important imaging modality in radiotherapy planning, magnetic resonance imaging (MRI)-only workflow, often realized via the generation of synthetic computed tomography (sCT), is desired due to superior soft-tissue contrast and less susceptibility to registration errors. PURPOSE: The aim of this study was to investigate the feasibility of applying sCT, generated from MRI using a deep learning model, to pelvic radiotherapy planning. By comparing differences between conventional CT and sCT in terms of image quality, dosimetric parameters, and three-dimensional (3D) dose distributions, the clinical potential of an MRI-only radiotherapy workflow was evaluated. METHODS: Fifteen patients who underwent both pelvic CT and MRI examinations were retrospectively enrolled. For the same patients, sCT images were generated from the MRI using a pretrained pelvic deep learning model integrated in the syngo.via VB60A software platform. Treatment plans originally created on planning CT (pCT) images were re-calculated on corresponding sCT datasets. Subsequently, the mean absolute error (MAE) of CT numbers, Dice similarity coefficients (DSCs) for major structures, dose-volume histogram (DVH) parameters for the planning target volume (PTV) and major organs at risk (OARs), and 3D dose distributions were compared between plans calculated on pCT and sCT. RESULTS: In terms of image quality, sCT demonstrated comparable CT number accuracy with pCT for soft tissue structures, with MAEs ranging from 6.8 to 8.5 Hounsfield units (HU) for the PTV, bladder, and rectum. Higher MAEs were observed for bony structures (femoral heads and bone marrow), with average MAEs ranging between 17 and 19 HU. The DSC was 0.94 ± 0.01 for the right femoral head, 0.93 ± 0.01 for the left femoral head, and 0.85 ± 0.03 for bone marrow. Regarding dosimetric comparison, the mean absolute differences in key dosimetric parameters for the PTV (D98%, D95%, and Dmean) were all below 0.6%, remaining within clinically acceptable limits. Among the OARs, except for relatively large differences for the maximum and minimum doses in the bladder, the mean dose (Dmean) differences for the rectum, femoral heads, and bone marrow were minimal (mean absolute value ≤ 0.34%), indicating high reliability. Analysis of 3D dose distributions using a 2% 2 mm γ criterion revealed an average γ passing rate of 95.92% between sCT and pCT, satisfying routine clinical quality assurance requirements. CONCLUSIONS: The findings of our study demonstrate the feasibility of applying sCT generated from MRI using a deep learning model to pelvic radiotherapy planning. The MRI-only workflow proposed on this basis eliminates systematic errors introduced by CT-MRI image registration, optimizes the clinical workflow, and fully exploits the superior soft-tissue contrast of MRI to improve target delineation accuracy. The proposed approach provides a novel technical paradigm for achieving more precise and efficient individualized radiotherapy.
Journal of applied clinical medical physicsDespoina Stasinou, Kalliopi Platoni, Vasiliki Margaroni, Kyveli Zourari, Emmanouil Zoros, Niko Papanikolaou, Evangelos Pappas
BACKGROUND: Single-isocenter stereotactic radiosurgery enables efficient treatment of multiple brain metastases (SI-MBM SRS), but demands high geometric accuracy. Plan complexity metrics are increasingly used as indicators for quality assurance (QA) performance, however their applicability to SRS remains uncertain, particularly in the context of multi-institutional variability. PURPOSE: This study evaluated the relationship between plan complexity, target geometry, and end-to-end dosimetric QA outcomes for SI-MBM SRS across multiple institutions. METHODS: Forty-two SI-MBM SRS plans from different centers and platforms were delivered to polymer gel phantoms, providing high-resolution 3D dose measurements. Gamma passing rates (GPRs) were calculated under 3%/2 mm, 5%/2 mm and 5%/1 mm criteria and were correlated with eleven established complexity metrics calculated per plan. Geometric factors, including target equivalent diameter and distance-to-isocenter, were analyzed. Receiver-operating-characteristic (ROC) analysis was performed to identify optimal thresholds for predicting QA pass/fail (≥90% GPR). RESULTS: No statistically significant differences between the different linacs and treatment planning systems were found, nor strong or consistent correlations between complexity metrics and GPRs. In contrast, geometric parameters were more influential: off-axis distance and target size significantly affected QA performance, with the largest differences observed for far-off-axis lesions. ROC analysis identified optimal thresholds of 34.9 mm for distance-to-isocenter and 4.8 mm for equivalent diameter in predicting QA outcomes (AUC∼0.60-0.65), although the predictive performance remained modest. CONCLUSIONS: In this multi-institutional, gel-based end-to-end study of SI-MBM SRS, target geometry was a stronger QA performance predictor than complexity metrics. These findings emphasize the importance of geometry-aware QA strategies and the need for further standardized, multi-institutional evaluations to clarify the interplay between complexity, geometry, and machine performance in SRS.
Cancer reports (Hoboken, N.J.)Xin Ran, He Xiao, Peng Zhou, Juan He, Mengyuan Si, Xiuqiong Chen, Xiaona Su, Zhuo Chen, Jia Du, Xiaoyan Dai, Xiao Yang, Haode Shen, Zongsheng He, Fan Li, Mengx…
BACKGROUND: Homologous recombination deficiency (HRD) has been reported to be associated with increased sensitivity to platinum-based treatment and radiotherapy in some solid tumors. AIM: This study investigated the correlation between HRD score and treatment response to neoadjuvant short-course radiotherapy combined with sequential chemotherapy and tislelizumab in mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC). METHODS AND RESULTS: Thirty-two pMMR LARC patients from clinical trial NCT05515796 were enrolled. Pretreatment biopsy samples were analyzed for HRD scores and tumor immune microenvironment (TIME) gene expression profiles. Using receiver operating characteristic (ROC) analysis, patients were stratified into low (0-8), intermediate (9-37), and high (> 37) HRD score groups to compare pathological complete response (pCR) rates. Abundance of immune cells and immune-related pathways were assessed with MCPcounter and single sample gene set enrichment analysis (ssGSEA) respectively and compared among the three HRD score groups. The entire cohort demonstrated pCR rate of 40.62% (13/32) with a median HRD score of 9 (range: 0-70). ROC analysis showed that HRD score as a continuous variable did not reach statistical significance in distinguishing pCR patients from non-pCR patients, nor did TMB and HR mutation. However, the proportion of categorized HRD score was significantly different between pCR and non-pCR groups (low, intermediate, high HRD score: 61.54%, 23.08%, 15.38% vs. 31.58%, 68.42%, 0%, p = 0.017). High-HRD tumors exhibited the highest CD8+ T-cell abundance followed by low-HRD and intermediate-HRD groups. CONCLUSION: HRD score may be associated with efficacy of neoadjuvant radioimmunotherapy in pMMR LARC patients, potentially mediated through enhanced CD8+ T-cell recruitment. These findings support precision patient selection, though mechanistic validation is required.
Journal of applied clinical medical physicsHideaki Hirashima, Takahiro Iwai, Shinya Hiraoka, Mitsuhiro Nakamura, Ryota Nakashima, Takashi Mizowaki
BACKGROUND: RapidArc Dynamic (RAD; Varian Medical Systems, Palo Alto, CA) is a novel volumetric modulated arc therapy (VMAT) technique that features dynamic collimator rotation synchronized with gantry rotation. RAD enables the use of static angle-modulated ports (STAMPs) defined by user selected gantry and collimator angles. However, the determination of STAMP configurations currently relies on manual trial-and-error procedures based on planner experience, which limits the efficient clinical implementation of this functionality. PURPOSE: This study aimed to develop an automated decision support tool using an Eclipse Scripting Application Programming Interface (ESAPI; Varian Medical Systems) to identify cost-optimized STAMP configurations and evaluate its clinical utility in complex head and neck cancer planning. METHODS: Twenty patients with nasopharyngeal or sinonasal cancer who had previously received radiotherapy at our institution were retrospectively analyzed. Four treatment plans were generated for each patient: conventional VMAT using RapidArc (RA, Varian Medical Systems), RAD with manually defined STAMPs (RADm) by an expert radiation oncologist, RAD with a vendor-provided automatic collimator rotation algorithm (RADa), and RAD using the proposed decision support tool (RADdst). The developed algorithm determined the STAMP configurations in three phases: (1) generation of a two-dimensional geometric cost map across the gantry and collimator angles by integrating planning target volume-fit and organ-at-risk (OAR)-avoidance terms, (2) extraction of a cost-minimizing collimator trajectory, and (3) identification of cost-optimized STAMP positions in geometrically critical regions that require substantial collimator rotation while satisfying machine-specific rotation-speed constraints. The dosimetric indices of the targets and OARs, optimization calculation times, and estimated beam delivery times were evaluated. RESULTS: The ESAPI-based tool successfully generated dosimetrically feasible RADdst plans for all patients, automatically selecting between two and ten STAMPs according to anatomical complexity. All planning techniques achieved clinically acceptable target coverage and OAR sparing. In nasopharyngeal cancer cases, all RAD approaches significantly reduced the oral cavity dose compared with RA (RADm, p = 0.02; RADa, p = 0.002; RADdst, p = 0.002), and RADdst additionally achieved a significant reduction in the left lens dose (p = 0.008). In sinonasal cancer cases, significant differences were observed among the techniques for seven OAR dosimetric metrics (p < 0.05), whereas the target coverage remained comparable across all techniques. The optimization calculation time was reduced by approximately 40% for all RAD approaches compared with RA (p < 0.01). Furthermore, all RAD techniques reduced the estimated beam delivery time by approximately 20% relative to RA (p < 0.01). CONCLUSIONS: An automated ESAPI-based decision support tool for STAMP configuration in RAD planning was successfully developed. The proposed geometric cost-based framework achieved a dosimetric performance comparable to both expert-defined manual STAMP planning and the vendor-provided automatic collimator rotation approach, while eliminating the need for manual STAMP determination. These findings support the feasibility of the automated STAMP configuration as a practical strategy for enabling an efficient and planner-independent implementation of RAD planning.
Journal of applied clinical medical physicsZeinab A Chahrour, Nour F Obeid, Ali El-Zaart, Wassila El Kanawati, Abbas Mkanna, Rida Assaf, Bilal H Shahine
BACKGROUND: Accurate CT/MR registration is important in stereotactic brain radiotherapy, where small spatial errors may affect target localization and treatment planning. In many clinical settings, registration quality is still assessed primarily through manual visual inspection. However, time and workflow constraints may limit the consistency and depth of manual evaluation. PURPOSE: This study aimed to develop a 3D convolutional neural network (3D CNN)-based quality assurance (QA) method for rigid brain CT/MR registration using paired sub-volumes and a registration-level mean probability score (μ). The proposed method classifies local CT/MR registration quality, while the final registration-level assessment is based on μ across the sampled sub-volumes. METHODS: The study included 209 patients. Of these, 202 comprised the primary cohort and were divided patient-wise into 128 training, 33 validation, and 41 test patients. For each patient, 25 skull-based CT/MR sub-volumes of 42 × 42 × 42 voxels were used as a two-channel CNN input. High-quality examples were obtained from clinically approved registrations, while low-quality examples were generated using rigid perturbations of the complete MR volume. The mean predicted probability across the 25 sub-volumes was used as the registration-level score μ, and the validation-derived threshold of 0.5871 was fixed for testing. Seven additional patients, separate from the 202-patient cohort, were evaluated after model development and threshold selection were completed using registrations before and after physician correction. RESULTS: On the held-out test set, patch-level accuracy was 85.90%, with an ROC AUC of 0.929 and average precision of 0.920. At the registration level, accuracy was 97.56% and ROC AUC was 0.999. All 41 low-quality registrations were correctly flagged, while 39 of 41 high-quality registrations were correctly accepted. In the additional clinical evaluation, all seven initial registrations requiring correction were classified as low quality, while six of seven corrected registrations were classified as high quality, resulting in an overall accuracy of 92.86%. CONCLUSIONS: The proposed method combined local CNN predictions into a registration-level μ score and showed strong performance on held-out and clinical cases. It may provide a quantitative screening measure for rigid brain CT/MR registration QA while maintaining clinical review as the final decision step.
Journal of applied clinical medical physicsKurtis H Dekker, Jennifer A Everaars
BACKGROUND: Single-isocenter multiple-target stereotactic radiation treatments delivered on C-arm linear accelerators are increasingly common due to practical advantages in both accessibility and speed compared to multiple isocenter treatments. Optimization of high-quality treatment plans can be a time-consuming process requiring substantial manual effort. In our institution, the planning workflow for these treatments was entirely manual and involved the generation of optimization structures and repeated recalculation and input of optimization objectives during the iterative optimization process. Although commercial automated planning solutions are available, their implementation may impose operational constraints, including reliance on specific immobilization and image/surface guidance hardware, motivating the development of an immobilization-independent automation tool for cranial stereotactic treatment plan optimization. PURPOSE: To develop and implement a treatment planning optimization tool for multiple-target cranial stereotactic treatments in the Varian Eclipse treatment planning system, to reduce manual planner input and planning time while improving plan quality. METHODS: A software tool was written using the Varian Eclipse Scripting Application Programming Interface to automatically generate target-specific ring structures and facilitate the iterative process of plan generation. Twenty cases were retrospectively re-planned with this tool and compared with the corresponding clinical plans to evaluate plan quality using qualitative and quantitative metrics of conformality and complexity. Automated plans were verified using portal dosimetry to ensure clinical deliverability. For ten cases, a timing study was performed to compare optimization time between the software tool and manual re-optimization. RESULTS: The automatic optimization tool produced plans with similar modulation and complexity, but consistently lower dosimetric falloff metrics (R50% and Paddick Gradient Index) than the corresponding clinical plans. All plans passed patient-specific QA (portal dosimetry) following institutional practice. For the ten cases included in the timing study, the software had a mean runtime of 5.8 min (range: 2-12 min), with variation depending on case characteristics such as number of targets and arcs employed. In comparison, manual plan generation required 21.5 min on average (range: 4-49 min). DISCUSSION: The automated planning tool produced clinically acceptable, deliverable plans with better dose falloff compared to the previous manual planning approach. The tool is estimated to save an average of 15 min of optimization time per plan. CONCLUSIONS: A treatment planning optimization tool has been developed that provides improvement in both dosimetric plan quality and treatment planning efficiency for single-isocenter multiple-target cranial stereotactic treatments.
Journal of applied clinical medical physicsLaurence E Court, Raphael Douglas, Parmeswaran Diagaradjane, Vindu W Kathriarachchi, Shiquin S, Ergys Subashi, Yao Zhao, Lifei Zhang, Tucker Netherton
PURPOSE: End-to-end AI-based automated contouring and radiotherapy planning systems promise substantial gains in efficiency and consistency but also introduce new safety risks, including user input errors that occur early in the workflow. This study evaluates the ability of standard physics plan review to detect user errors in prescription and planning target volume (PTV) margin entry in a fully automated planning workflow. METHODS: A prototype of the Radiation Planning Assistant (RPA) was used to generate fully automated prostate cancer treatment plans for 20 patients. Five cases intentionally included incorrect prescriptions or non-standard PTV margins. Five clinical medical physicists independently performed physics plan reviews in a commercial treatment planning system, assuming a standard clinical workflow and without access to user guides or service request forms. Reviews were conducted in two phases, with and without margin information embedded in structure names. A third phase evaluated whether adding reference expansion structures improved margin error detection. RESULTS: Incorrect prescriptions were detected in 80% of cases, with no false-positive identification of correct prescriptions. In contrast, detection of incorrect PTV margins was highly inconsistent. Two physicists did not evaluate margins and missed all margin errors. Three physicists identified all intentional margin errors but demonstrated poor specificity, frequently flagging correct cases as incorrect (specificity range: 13%-63%). Including margin information in structure names and adding reference expansion structures did not improve specificity or overall detection performance. CONCLUSIONS: Physics plan review was unreliable for detecting incorrect PTV margins in a fully automated planning workflow, even when additional cues were provided. Although based on a limited dataset, these findings indicate that traditional plan review processes alone are insufficient to mitigate this failure mode. Alternative risk-reduction strategies-such as timely workflow-embedded alerts, targeted checklists, automated verification tools, and careful expectation setting-are likely required to improve safety in AI-driven radiotherapy planning systems.
Journal of applied clinical medical physicsRoya Barati, Jingwei Duan, Song Gao, Yao Zhao, Xinru Chen, Cenji Yu, Zhan Xu, Moghadaseh Khaleghibizaki, Fredrik Lofman, Jared Ohrt, Laurence Court, Peter Balt…
BACKGROUND: Commercial deep-learning segmentation (DLS) tools are increasingly used in clinical practice. Software updates may alter segmentation performance, highlighting the need for systematic clinical evaluation before implementation. PURPOSE: This study presents our experience in clinically evaluating and regression-testing a RayStation DLS model with the aim of guiding commissioning and routine quality assurance of commercial DLS tools in clinical environments. METHODS: U-Net DLS model for normal-tissue structures, originally commissioned in RayStation version 11B, was regression-tested after upgrading to 2024A. Previously commissioned CT datasets for head and neck (n = 18), thorax (n = 18), male pelvis (n = 18), and breast (n = 21) were re-evaluated in RayStation 2024A for regression testing following the software upgrade, while 20 new abdominal cases were included for initial commissioning. Clinical segmentations served as the reference standard. Geometric performance was evaluated using Dice Similarity Coefficient (DSC), 95% Hausdorff Distance (HD95), and Mean Surface Distance (MSD). Dosimetric evaluation used the original clinical treatment plans to compare Dmean and Dmax between DLS and clinical contours, normalized to prescription dose; breast was excluded from dosimetric analysis because its DLS model was not commissioned for clinical use. RESULTS: Regression testing showed that, in comparison with the previously commissioned data, mean [± standard deviation (SD)] DSC values were 0.81 ± 0.09 for the head and neck, 0.84 ± 0.13 for the thorax, and 0.89 ± 0.06 for male pelvis. Corresponding MSD values were 0.83 ± 0.34 mm, 2.47 ± 1.81 mm, and 1.76 ± 0.68 mm; and HD95 values were 4.75 ± 2.38 mm, 8.45 ± 3.38 mm, and 13.21 ± 7.05 mm. Significant paired differences between versions were limited to selected structures, including the mandible, cochlea, and eye in head and neck; lungs and esophagus in thorax; and prostate in the male pelvis (p < 0.05). Breast segmentation results showed low performance (DSC 0.66 ± 0.15, MSD 4.8 ± 1.93 mm, and HD95 22.2 ± 9.6 mm) compared to clinical reference, so the breast structure models are not recommended for clinical use. Abdominal structures (RayStation 2024A vs clinical) had DSC 0.95 ± 0.014; MSD 0.82 ± 0.32 mm; and HD95 5.4 ± 2.9 mm. The mean dose differences between DLS and clinical segmentations were 0.03 Gy for the head and neck, -0.92 Gy for the thorax, 0.27 Gy for the male pelvis, and 0.02 Gy for the abdominal sites, and the corresponding maximum dose differences were 10.96 Gy, 13.23 Gy, 3.39 Gy, and 6.31 Gy. CONCLUSIONS: We described a procedure for practical quality assurance of auto-segmentation tools for clinical use after periodic software upgrades. Regression testing of head and neck, thorax, and male pelvis sites showed consistent performance after the software upgrade and the DLS models for abdominal site were commissioned in this study for clinical use; while the DLS models for breast site were not recommended.
Journal of applied clinical medical physicsOfformata E Osunkwor, Alois Ndlovu, Roland F Teboh
BACKGROUND: Respiratory motion introduces significant geometric uncertainty in Stereotactic Body Radiotherapy (SBRT) for thoracic and abdominal tumors. Deep Inspiration Breath-Hold (DIBH) mitigates this, but the surface signal alone may not reflect internal target position, supporting the need for real-time internal-anatomy verification during delivery. PURPOSE: To commission a Surface-Guided Radiation Therapy (SGRT) system and validate an integrated SGRT + Image-Guided Radiation Therapy (IGRT) + triggered kV imaging (SITI) workflow for DIBH SBRT. MATERIALS & METHODS: The LAP LUNA 3D SGRT system was commissioned per AAPM TG-302 using phantom-based assessment of static and dynamic localization accuracy, reproducibility, and latency. An end-to-end test using a dynamic phantom validated the SITI workflow. Point dose was measured with an ion chamber under four scenarios: SGRT-only delivery, full SITI delivery, and SITI with induced 1 and 2 mm uncorrected 3D shifts. RESULTS: Static localization accuracy was better than 0.5 mm / 0.3°, with reproducibility within 0.2 mm / 0.1°. Dynamic testing confirmed sub-millimeter spatial accuracy and a 31.6 ms latency, well below the AAPM TG-302 100 ms tolerance. The 1 and 2 mm uncorrected shifts produced point-dose reductions of 0.9% and 2.2% relative to the SITI reference, consistent with the ∼1%/mm local dose gradient. Both shifts were clearly visualized on triggered kV images, confirming detection of sub-tolerance residual displacements undetected by surface guidance alone. CONCLUSIONS: The LAP LUNA 3D system meets the technical requirements for SBRT. The SITI workflow is technically feasible and provides real-time visualization of internal target position during delivery, offering a robust motion-management strategy for DIBH SBRT of mobile thoracic and abdominal targets.
Journal of applied clinical medical physicsMizuha Sakai, Megumi Nakao, Hideaki Hirashima, Masahiro Yoneyama, Noriko Kishi, Takashi Mizowaki, Mitsuhiro Nakamura
BACKGROUND: Deformable image registration (DIR) is essential for thoracic four-dimensional computed tomography (4D-CT)-based radiotherapy applications. Recently, deep learning-based DIR methods such as VoxelMorph have been proposed; however, their performance relative to clinically used DIR algorithms remains unclear. PURPOSE: This study aimed to evaluate the DIR accuracy of VoxelMorph for thoracic 4D-CT and to compare it with conventional clinical and research-oriented DIR methods. MATERIALS AND METHODS: Thoracic 4D-CT data from 64 lung cancer patients were retrospectively analyzed. End-inhalation and end-exhalation phase images were used for DIR. VoxelMorph was trained using 50 cases, with 4 for validation and 10 for testing. DIR performance on the test dataset was compared with Demons (SimpleITK), modified Demons (Eclipse), and ANACONDA (RayStation). Accuracy was evaluated by mean absolute error (MAE) of CT values computed within the body region, whereas Dice similarity coefficient (DSC) and 95th percentile of Hausdorff distance (HD95) were evaluated within the lung label. RESULTS: The median MAE decreased from 67.56 HU before DIR to 52.32 HU with modified Demons, 37.39 HU with Demons, 36.18 HU with ANACONDA, and 36.83 HU with VoxelMorph. The median DSC increased from 0.91 to 0.95 for modified Demons, 0.97 for Demons and ANACONDA, and 0.98 for VoxelMorph. The median HD95 was 3.0 mm for modified Demons, 3.1 mm for Demons, 2.0 mm for ANACONDA, and 2.5 mm for VoxelMorph. Overall, VoxelMorph demonstrated competitive accuracy, significantly outperforming modified Demons (adjusted p < 0.05), while showing smaller inter-case variability and markedly reduced processing time. CONCLUSIONS: VoxelMorph demonstrated DIR performance comparable to that of clinically used algorithms for thoracic 4D-CT, with high overlap accuracy, relatively low inter-case variability and shorter processing times under the evaluated implementation conditions. These findings suggest its potential as research-oriented DIR framework, although further validation under standardized conditions is required before routine clinical implementation.
Radiation oncology (London, England)Sebastian Regnery, Rita Pestana, Thomas Mielke, Philipp Hoegen-Saßmannshausen, Hanna Waldsperger, Fabian Weykamp, Friderike K Longarino, Cedric Beyer, Jakob Li…
BACKGROUND: We aim to quantify the dosimetric benefits of daily online adaptive (DOA) carbon ion stereotactic radiotherapy (CISR) in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: 13 patients received 4 × 10.5 Gy (RBE-weighted dose) CISR to 14 HCC lesions in challenging locations (N = 10: liver dome, N = 3: < 1 cm from intestines). All patients underwent daily in-room CT, with forward calculation of the baseline plan. Additionally, four patients were shuttled to a 1.5 Tesla MR scanner in treatment position for MRI simulation. Based on visual review of all data, the physician decided to treat or to perform offline plan adaptation and treat another day. We compare the dosimetry properties of four scenarios per fraction: (1) baseline plan, (2) no adaptation, (3) occasional offline adaptation (OOA), (4) DOA. RESULTS: Baseline planning target volume (PTV) and internal target volume (ITV) coverage by the prescribed dose (median coverage: PTV: 97%, ITV: 100%) significantly decreased for no adaptation (PTV: 87.6%, p = 0.0001; ITV: 97.7%, p = 0.007) and OOA (PTV: 87.8%, p = 0.0001; ITV: 97.7%, p = 0.007), while DOA maintained high PTV coverage (PTV: 95.7%, p = 0.17; ITV: 100%, p = 0.53). Frequent violations of organs-at-risk (OAR) dose constraints occurred for no adaptation and OOA (both 20/52 fractions, 38.5%). They affected the bowel, heart and esophagus up to 6 cm from the PTV. DOA led to considerably fewer (6/52 fractions, 11.5%) and less intense violations of OAR dose constraints. CONCLUSIONS: Daily CT- and MR-guided CISR is feasible in the liver, and demonstrates frequent violations of initial treatment planning objectives when non-adaptive or offline adaptive approaches are followed. DOA could improve target coverage and OAR protection, while particularities of carbon ions such as overdoses far from the target should be considered.
Medical physicsFrances Kan, Freeman Jin, Adam Mylonas, Benjamin Zwan, Trang Nguyen, Trevor Moodie, Nicholas Hardcastle, Sau Fan Liu, Daniel Mason, Tim Wang, Yoo Young Lee, Pa…
BACKGROUND: During radiation therapy, liver tumor motion can reduce dose delivery accuracy and increase irradiation of adjacent healthy tissues. Because liver tumors are difficult to visualize directly on kilovoltage (kV) X-ray images, fiducial markers are commonly implanted as surrogates for tumor position during treatment. Conventional marker-segmentation approaches such as template matching can lose accuracy when markers are obscured by bone, surgical clips, or stents. Although Convolutional Neural Network (CNN)-based approaches have shown strong performance for image analysis, their application has been constrained to more static organs such as the prostate or has used single-center and vendor-specific datasets, limiting assessment of model transportability across different institutions and anatomic sites. PURPOSE: The aim of this study was to develop, integrate, and evaluate a CNN-based method for fiducial marker detection in kV X-ray images to support real-time image-guided radiation therapy (IGRT) during liver radiotherapy using a multi-institutional, multi-platform dataset spanning both large and fast free-breathing motion and slow and small breath-hold motion. METHODS: A compact Convolutional Neural Network (CNN) was trained on 314,625 kilovoltage (kV) X-ray images encompassing 28 patients from the multi-institutional TROG 17.03 LARK clinical trial (NCT02984566). The model was validated using a hold-out set of 31,463 images (10%) from the same cohort of 12 patients and 55 treatment fractions, spanning three centers and three respiratory motion-management techniques. The CNN was tested on 4184 images from 16 patients and 55 fractions across three centers and three motion-management techniques. The ground truth for testing was manually segmented marker positions from every 10 degrees of gantry rotation for each fraction of each test patient. Based on AAPM guidelines (TG147 and TGB135.B), feasibility for clinical implementation was predefined as > 95% of marker positions being within 2 mm of the ground truth position in each dimension, and processing time less than 150 ms per image using a simulated real-time Kilovoltage Intrafraction Monitoring (KIM) framework. Additional evaluation metrics included sensitivity, specificity, and the area under the precision-recall curve (AUC). RESULTS: For the unseen test patient data, the marker position was segmented by the CNN within 2 mm in 95.4% of frames on the X axis and 97.6% of frames on the Y axis, meeting AAPM criteria. Sensitivity reached 97.76%, specificity was 99.94%, and the AUC was 0.9964. No statistically significant difference in localization error was observed between breath-hold and free-breathing treatments, although this comparison was limited by the small number of free-breathing patients. Localization error differed significantly between Varian and Elekta linacs due to imbalance within the dataset. The processing time for each image was 50-60 ms using a NVIDIA GeForce RTX 3070 GPU. CONCLUSION: A CNN-based method for fiducial marker detection in the liver was developed and evaluated on multi-institutional kV X-ray images spanning free-breathing and breath-hold motion, as well as Varian and Elekta linac platforms. The method satisfied the predefined feasibility criteria for positional accuracy and computation time, supporting future translation toward clinical implementation.
Journal of applied clinical medical physicsHilla Magga, Henri Korkalainen, Tuomas Virén, Janne Heikkilä, Jan Seppälä, Akseli Leino
BACKGROUND: Deep learning-based (DL) approaches have gained interest in predicting dose distributions in radiotherapy of prostate cancer treated with volumetric modulated arc therapy and intensity-modulated radiation therapy. Meanwhile, research on predicting dose distributions in high-precision stereotactic radiotherapy treatments has remained relatively underrepresented. PURPOSE: We aimed to expand the previous studies by developing a DL-based framework for predicting dose distributions for robotic, stereotactic prostate cancer radiotherapy. METHODS: We harnessed a U-Net-based convolutional neural network for predicting clinically achievable dose distributions based on CT images, delineated structures, and distance information from the planning target volume. A dataset of 462 patients treated with CyberKnife (Accuray Inc.) utilizing an Iris collimator was divided into training (70%, n = 323), validation (10%, n = 46), and test (20%, n = 93) sets. RESULTS: In the independent test set, the mean absolute error between the mean doses of predictions and clinical plans was 0.63 Gy for the rectum and 1.04 Gy for the bladder. CONCLUSIONS: The proposed U-Net-based model demonstrated the ability to learn and reproduce characteristic dose distributions in CyberKnife prostate cancer radiotherapy. The model may provide patient-specific dose estimates for setting initial planning objectives to assist in automating treatment planning and improving inter-planner consistency.
Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy SocietyKeiichiro Nakajo, Yu Sasagawa, Takuro Tomino, Haruto Hirose, Atsuki Imai, Minami Endo, Hiroki Yamashita, Masataka Yamamoto, Hiroshi Takemura, Tomonori Yano
OBJECTIVES: Approximately 12%-40% of patients with esophageal cancer develop local residual or recurrent lesions after chemoradiotherapy (CRT) or radiotherapy (RT). Photodynamic therapy (PDT) is a minimally invasive, organ-preserving alternative; however, therapeutic response is not guaranteed. We developed an artificial intelligence (AI) model to predict PDT efficacy. METHODS: We retrospectively analyzed 177 patients who underwent PDT after CRT/RT at the National Cancer Center Hospital East between August 2006 and December 2024. Clinical data and pre-PDT endoscopic images obtained within 1 month were collected. Local image features extracted via oriented FAST and rotated BRIEF were integrated with clinical information to build a multimodal support vector machine for binary classification. Model performance was evaluated on an independent test set and compared with that of three endoscopists. RESULTS: The AI model was trained on 145 cases, achieving an accuracy, recall, precision, and F1 score, and area under the receiver operating characteristic curve of 0.813, 0.833, 0.833, 0.833, and 0.897, respectively in the test cohort of 32 cases. The AI model showed numerically higher accuracy, recall, precision, and F1 score than the endoscopists (0.531, 0.636, 0.389, and 0.483, respectively). CONCLUSIONS: A multimodal AI model integrating clinical data and endoscopic images can accurately predict PDT efficacy after CRT or RT. This approach may help optimize treatment strategies and individualize patient management.
Journal of applied clinical medical physicsAmritpal Singh, Raffi Karshafian, Ananth Ravi, Moti Raj Paudel
BACKGROUND: The knowledge of the dosimetric impact of systematic source position uncertainty and the use of a methodology for robust treatment planning against such uncertainty can help improve the quality of treatment plans, during MR-only cervical brachytherapy treatment. PURPOSE: To assess the dosimetric impact of systematic source position uncertainty along the source path and evaluate strategies to minimize it during MRI-only cervical high-dose-rate (HDR) brachytherapy treatment planning. METHODS: Treatment plans from 22 cervical cancer patients (FIGO stages IB2-IVA; 11 intracavitary brachytherapy (ICBT), 11 interstitial brachytherapy (ISBT)) were retrospectively analyzed. Positional uncertainty was modeled by systematically shifting the source position (± 1 to ± 5 mm with 0 mm as the reference position) within applicators along the source path in the original plans. Dosimetric parameters, HRCTV_D90 and D2cc for organs at risk (OARs), were computed for each source position. Statistical significance was assessed via paired t-test and Wilcoxon signed-rank test. Targeted plans exceeding dosimetric limits for OARs were re-optimized by modifying dwell times or gradients within 1 cm of the targeted OAR to improve the variability and overall OAR dosimetry. RESULTS: Significant dosimetric changes were observed for bladder, sigmoid (all shift positions; p ≤ 0.001) and rectum (1 to 5 mm; p ≤ 0.04) in ICBT, and for all OARs (all shift positions; p ≤ 0.003) in ISBT. HRCTV_D90 was significantly affected in ICBT from -2 to -5 mm (p ≤ 0.042) and at all shifts (p ≤ 0.033) except at -1 and -2 mm in ISBT. Within ± 5 mm shift range, the mean (maximum) drop in HRCTV_D90 and increase in OARs (bladder, bowel, rectum and sigmoid) D2cc were up to -2.0 ± 1.9(-5.4)% and (6.0 ± 3.4(13.6)%, 0.5 ± 2.5(5.5)%, 2.2 ± 2.7(7.4)% and 1.8 ± 1.2(4.2)%) for ICBT, and -6.2 ± 1.4(-11.9)% and (5.2 ± 4.6(17.2)%, 1.3 ± 0.9(3.0)%, 4.6 ± 2.5(7.6)% and 6.6 ± 3.6(13.8)%) for ISBT, respectively. Re-optimized plans showed improved robustness of dosimetry against source positional uncertainty for the targeted OAR with the same or better dosimetry for other OARs and HRCTV. The strategies to obtain this robustness were patient and applicator-type dependent. CONCLUSION: Systematic source position uncertainty significantly influences dosimetry in MRI-only cervical HDR brachytherapy. Adjusting dwell times and gradients near the targeted OAR could minimize this effect.
BMJ openJin Li, Nianlan Zhou, Saiquan Lu, Xi Yang, Wangjun Yan, Zhengfei Zhu, Mo Cheng
INTRODUCTION: Immunotherapy in combination with chemotherapy has been recommended as the first-line treatment of driver gene-negative advanced non-small cell lung cancer (NSCLC), but the efficacy is reduced in NSCLC patients with bone metastases due to the immunosuppressive microenvironment. Both nuclear factor kappa-B ligand (RANKL) inhibitors and stereotactic body radiation therapy (SBRT) have been shown to modulate the tumour immune microenvironment. Therefore, narlumosbart, a monoclonal antibody targeting RANKL, in combination with SBRT, may exert synergistic effects and improve efficacy of first-line chemoimmunotherapy in this population. METHODS AND ANALYSIS: This single-arm, single-centre phase II clinical trial will enrol driver gene-negative advanced NSCLC patients with bone metastases who have not received any systemic therapy. Eligible patients will receive narlumosbart (120 mg subcutaneously every 4 weeks) and SBRT to bone target lesions (24 Gy/3 fractions for spinal metastases and 30-35 Gy/5 fractions for non-spinal lesions), followed by standard first-line chemoimmunotherapy. The primary endpoint is the objective response rate of non-radiotherapy lesions. Secondary endpoints include safety and tolerability, progression-free survival, overall survival, bone-related events, pain score and quality of life. Sample size was calculated using the Simon's Two-Stage method (α=0.05, power=0.8, H₀=25%, H₁=50%). Nine patients will be enrolled in stage 1. If ≥2 patients achieve complete response (CR)/partial response (PR), an additional 15 patients will be enrolled in stage 2. If fewer than two patients achieve CR/PR, the trial will be terminated. 27 subjects will be enrolled in this project, considering the dropout rate of 10%. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethics Committee of Fudan University Shanghai Cancer Center (approval number 2411308-15) on 6 December 2024. The trial registration number is NCT06738160 at clinicaltrials.gov, sponsored by Fudan University, and registered in December 2024 before the enrolment of the first participant in February 2025. The trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent will be obtained from all participants prior to enrolment. Results will be published in a peer-reviewed journal.
Medical physicsHongkai Wang, Wenzheng Sun, Wenlong Xia, Bin Liang
BACKGROUND: Conventional volumetric modulated arc therapy (VMAT) optimization relies on gradient-based methods in which analytical gradients must be explicitly derived for each objective function and machine constraint. This dedicated mathematical derivation imposes substantial barriers to extending the optimization framework with new clinical objectives or delivery constraints, and the resulting CPU-based implementations do not natively exploit modern GPU hardware. PURPOSE: To develop an end-to-end differentiable VMAT optimization framework using computation graphs that enable automatic differentiation-based gradient computation for both fluence map optimization (FMO) and direct aperture optimization (DAO), while incorporating VMAT machine delivery constraints within a unified, GPU-accelerated pipeline. METHODS: A two-stage pipeline-fluence map optimization (FMO) followed by DAO-was developed. FMO reformulates dose calculation as a differentiable computation graph, enabling gradient computation for arbitrary objective functions including non-smooth Heaviside step terms. For DAO, a novel analytically derived computation graph maps MLC leaf positions to delivered fluence through closed-form time-averaged bixel exposure integration with finite-width boundary corrections, ensuring exact differentiability. Machine delivery constraints-including leaf collision, speed limits, and dose rate bounds-are incorporated as differentiable penalty terms for joint end-to-end optimization. Twenty lung cancer cases from the GDP-HMM AAPM Challenge dataset (60 Gy/30 fractions) were optimized using objectives derived from clinical Eclipse reference plans and compared against MatRad and Eclipse. RESULTS: The proposed method achieved PTV D98 of 58.88 ± 0.33 Gy, comparable to Eclipse (59.07 ± 0.55 Gy, p = 0.26) and significantly higher than MatRad (57.27 ± 0.48 Gy, p < 0.001). The Paddick conformity index was 0.81 ± 0.06, comparable to Eclipse (0.84 ± 0.22, p = 0.48) and superior to MatRad (0.64 ± 0.11, p < 0.001). OAR sparing closely matched Eclipse: heart mean dose 10.74 ± 4.89 Gy vs. 11.55 ± 4.76 Gy; lung mean dose 15.33 ± 3.50 Gy vs. 16.70 ± 3.29 Gy; LAD mean dose 9.55 ± 4.97 Gy vs. 9.05 ± 3.94 Gy (p = 0.18). MatRad achieved lower heart doses at the cost of degraded PTV coverage and conformity. Optimization time was significantly shorter (59.28 ± 43.95 s vs. 390.30 ± 184.90 s, p < 0.001), while delivery times were equivalent (p = 0.92). CONCLUSIONS: The proposed differentiable VMAT framework demonstrated superior goal-directed optimization fidelity compared with MatRad-more reliably translating objectives into intended dosimetric outcomes-achieving plan quality approaching clinical Eclipse plans with faster optimization.
Journal of applied clinical medical physicsEdward A Opalko, Dheerendra Prasad, Matthew B Podgorsak
PURPOSE: The purpose of this study was to evaluate the ability of the GammaPlan treatment planning system used in the Gamma Knife Icon and Esprit machines to automatically correct large interfractional shifts in hypofractionated frameless treatments using a custom 3D printed phantom. METHODS: A custom 3D printed insert was created to modify a commercial head phantom. The water equivalence of polylactic acid (PLA) was determined by comparing optical densities of film using solid water and PLA as buildup. Lesions of varying size, shape and location were created on images of the phantom to replicate several clinical scenarios. Seven 5-fraction plans were generated using typical dose objectives. Six combinations of headrests/masks were created to simulate different setup positions. Masks were changed between fraction measurements to simulate interfractional shifts. The composite dose distributions of the corrected plans were measured using Gafchromic film and compared to the original dose distribution using Gamma Analysis. RESULTS: The average deviation for Coverage, Paddick Conformity Index and Gradient Index across all plans remained unchanged between the corrected plan and the original plan. No deviation was greater than 0.01 between the three metrics. Compared to the original plans, the measured dose distributions produced an average Gamma Passing Rate of 98.3% for 3%/1mm, 99.6% for 2%2mm, 96.3% for 2%1mm and 92.7% for 1%/1mm. All but two dose distributions produced passing rates above 90%. For the dosimetric analysis of PLA, the optical densities at various MU values were found to be equivalent for solid water and PLA. CONCLUSION: The correction algorithm was able to produce a corrected plan almost identical to the original plan in terms of plan statistics and dose distributions. The algorithm could accurately correct for extreme interfractional shifts beyond what is seen clinically. The results of this study also show the potential for PLA phantoms to be used as dosimetry tools.
Biomedical physics & engineering expressSali Di, Brandon VanGenderen, Marcus Sonier, Joseph Awotwi-Pratt
Stereotactic body radiotherapy (SBRT) for prostate cancer often uses high-energy photon beams, which can produce photoneutrons through interaction in the linac head, raising concerns regarding neutron-related exposure. Therefore, it is important to estimate neutron dose equivalent in SBRT plans when comparing beam energies and treatment delivery techniques. BD-PND fast neutron detectors were used in this study to quantify neutron dose equivalent in prostate SBRT plans. We performed dosimetry measurements using a Varian TrueBeam Linac and assessed neutron production at energies of 2.5 MV, 6 MV, 6 MV flattening filter free (FFF), 10 MV, 10 MV FFF and 15 MV. Bubble counts were converted to neutron dose equivalent using the manufacturer-provided calibration factor. The measured neutron dose equivalent was highest at the centre and decreased at peripheral measurement locations farther from the primary beam. Significant differences in neutron dose equivalent were found between flattening filter (FF) and FFF beams at the central beam position after multiple comparison correction. In contrast, peripheral positions showed no statistically significant differences. Additionally, low bubble counts were observed under 6 MV and 6 MV FFF beams, suggesting a low-level detector response under the present measurement conditions. Overall, beam energy, FF or FFF delivery and measurement positions all affect the measured neutron dose equivalent in prostate SBRT. The low-energy observation should be interpreted as preliminary, and additional work is needed, including repeated measurements, different detector types and more clinically relevant measurement locations.
BACKGROUND: Image-guided radiotherapy (IGRT) using cone-beam computed tomography (CBCT) enables highly accurate imaging registration; however, increased radiation exposure remains a concern. Recently, short-arc CBCT (SA-CBCT), which reduces projection data and reconstructs images, has become available. Although previous studies have shown that image quality deteriorates when projection data are reduced, no study has directly evaluated the clinical usefulness of SA-CBCT or its effect on registration accuracy. PURPOSE: We verified the registration accuracy of SA-CBCT in breast tangential irradiation using an anthropomorphic phantom and clinical data, and examined its clinical feasibility compared with the commonly used 200° scan. METHODS: An anthropomorphic phantom was placed on the treatment bed, and CT and CBCT images acquired during treatment planning were aligned. Bed movement was measured for both conventional CBCT and SA-CBCT images. The difference between the two measurements was quantified as N, defined as the norm of the vector difference between CBCT and SA-CBCT registration shifts, to evaluate registration accuracy. The acquisition angle was varied to assess the effects of central and total angles. In the clinical study, registration data from 30 consecutive patients who underwent whole-breast irradiation were analyzed. Data were reconstructed by changing the acquisition angle from 200° to 120°, and N was calculated as in the phantom experiment. RESULTS: In the phantom experiment, N was within 0.15 mm (3-axis) and 0.55 mm (6-axis) when the acquisition angle was reduced to 120°. In clinical data, the average N was 0.64 mm in 3-axis registration (84.7% within 1 mm) and 0.85 mm in 6-axis registration (71.3% within 1 mm). Even with a 120° acquisition angle, the body contour and chest wall edges were sufficiently preserved. CONCLUSIONS: SA-CBCT maintained adequate registration accuracy in breast tangential irradiation. These findings suggest its clinical applicability with appropriate acquisition angle settings.
Journal of applied clinical medical physicsCarolyn Eckrich, Kristin Bradley, Bethany Anderson, Diego Hernando, Jessica Miller, Jainil Shah, Patrick Wohlfahrt, Michael Lawless
BACKGROUND: Pelvic external beam radiation therapy (EBRT), frequently exposes a substantial fraction of active bone marrow (ABM), leading to radiation-induced marrow suppression and associated hematologic toxicity. Accurate delineation and quantitative assessment of ABM are therefore essential to enable marrow-sparing radiotherapy strategies. PURPOSE: To identify and quantify changes in ABM after EBRT using multi-energy CT (MECT) and fat fraction MRI (FFMRI). METHODS: Patients with gynecological malignancies underwent MECT and FFMRI pre- and post-radiation therapy. ABM was delineated on both imaging modalities using thresholding where ABM was defined as voxels with CT numbers above the mean in MECT-derived virtual non-calcium (VNCa) datasets and voxels with percent fat fraction (%FF) below the mean on the FFMRI. ABM volumes and mean HU/%FF values were evaluated before and after treatment. A Wilcoxon-signed rank test was computed to compare paired MECT versus FFMRI ABM volume percent changes. Changes in ABM as a function of dose were also evaluated. A paired t-test was computed for each dose gradient (significant p < 0.05). RESULTS: The average Dice Similarity Coefficient (DSC) between the MECT and FFMRI pre-treatment ABM volumes was 0.57 (range: 0.50-0.68). The mean volumetric change in ABM volume between pre- and post-treatment scans was -37% ± 15% (range -57% to -12%) and -66% ± 27% (range 8% to -94%) for MECT and FFMRI, respectively. All paired patients demonstrated greater ABM volume reduction with FFMRI than with MECT, and this difference was statistically significant (p = 0.0078). ABM changes were observed as a function of dose: A decrease in mean CT numbers and an increase in %FF corresponds to an increase in dose. CT number decreased significantly at doses ≥10 Gy (p ≤ 0.005), while %FF increased significantly across all dose gradients (p ≤ 0.0017), with both metrics showing strong dose‑response behavior at higher doses (p < 10- 6). CONCLUSIONS: This feasibility study demonstrates the utility of using MECT and FFMRI for delineating ABM in patients receiving pelvic EBRT. These imaging modalities showed good agreement in characterizing ABM volumes changes and radiation-induced marrow suppression. These findings support further investigation of ABM segmentation into the RT-planning workflow to facilitate marrow-sparing strategies.
Anticancer researchFederico Ampil, Robert Brown, Michelle Norton
BACKGROUND/AIM: Hippocampal brain metastases are uncommon, and evidence regarding their management and outcomes remains limited. This study evaluated the efficacy and safety of whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for hippocampal brain metastases at a single institution. PATIENTS AND METHODS: We retrospectively reviewed 21 patients treated for hippocampal brain metastases over a 20-year period. Clinical characteristics, treatment approaches, intracranial tumor control, treatment-related toxicity, and survival were analyzed. Eleven patients received WBRT and 10 received SRS. RESULTS: The mean patient age was 60.7 years. Most patients were symptomatic (86%), had multiple brain metastases (71%), and had extracranial metastatic disease (76%). Memory impairment was documented in one patient. Among patients receiving WBRT, contralateral hippocampal avoidance was not feasible in five (45%) because of multiple brain metastases. The mean follow-up was 17.2 months. Intracranial tumor control was achieved in 18 patients (86%), and radionecrosis occurred in one patient (5%). The overall median survival was four months, and the estimated one-year survival rate was 42%. Intracranial tumor control rates were 91% after WBRT and 80% after SRS (p=0.49); the corresponding median survival times were one and five months, respectively (p=0.29). No acute or chronic treatment-related toxicity was documented, although post-treatment neurocognitive function was not systematically assessed. CONCLUSION: WBRT and SRS provided high rates of intracranial tumor control with limited observed toxicity in this small cohort of patients with hippocampal brain metastases. However, overall survival remained poor. Larger studies incorporating standardized neurocognitive assessment are needed to clarify the comparative benefits and long-term safety of these treatment approaches.
The Lancet. OncologyGuang-Yi Sun, Si-Ye Chen, Yu Tang, Hui Fang, Yong-Wen Song, Yue-Ping Liu, Jing Jin, Ning Li, Ning-Ning Lu, Yuan Tang, Shu-Nan Qi, Bo Chen, Hao Jing, Yi-Rui Zha…
BACKGROUND: Hypofractionated radiotherapy is an established alternative to conventional fractionation for breast cancer, but long-term evidence after mastectomy with regional nodal irradiation is scarce. We aimed to assess the long-term efficacy and adverse event profile of hypofractionated versus conventional fractionated postmastectomy radiotherapy in high-risk breast cancer. METHODS: This randomised, non-inferiority, open-label, phase 3 trial was done at a national cancer centre in China. Eligible patients were women aged 18-75 years with high-risk breast cancer who had undergone modified radical mastectomy and axillary dissection with a Karnofsky performance score 60% or higher. Participants were randomly assigned (1:1) to conventional fractionated radiotherapy (50 Gy in 25 fractions over 5 weeks) or hypofractionated radiotherapy (43·5 Gy in 15 fractions over 3 weeks) to the chest wall and supraclavicular region, using a computer-generated sequence with concealed allocation and no masking. The primary endpoint was 5-year cumulative incidence of locoregional recurrence, analysed in the modified intention-to-treat population (including all eligible patients who underwent randomisation, but excluding those who were considered ineligible or withdrew consent after randomisation) and a 5% margin was used to establish non-inferiority. In this prespecified long-term analysis, outcomes at 10 years were analysed without additional confirmatory non-inferiority testing. Safety was analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT00793962, and is closed to enrolment. FINDINGS: Between June 12, 2008, and June 16, 2016, 2157 patients were assessed for eligibility. 1337 were excluded and 820 patients were enrolled and randomly assigned (414 to conventional fractionated radiotherapy and 406 to hypofractionated radiotherapy). Five patients were excluded in each group and 810 were included in the analyses (409 to conventional fractionated radiotherapy and 401 to hypofractionated radiotherapy). Median follow-up was 11·5 years (IQR 9·6-13·8). Median patient age was 49 years (range 24-74), and 761 (94%) patients had stage III disease. All patients were female, and data on race and ethnicity were not collected. At 10 years, cumulative locoregional recurrence was 10·3% (95% CI 7·3-13·3) with conventional fractionated radiotherapy and 12·0% (8·8-15·2) with hypofractionated radiotherapy (hazard ratio 1·19, 95% CI 0·79-1·82). The most common grade 3 adverse events at 10 years were ischaemic heart disease (five [1%] of 409 patients in the conventional fractionated radiotherapy group vs five [1%] of 401 patients in the hypofractionated radiotherapy group), lymphoedema (four [1%] vs three [<1%]), shoulder dysfunction (two [<1%] vs one [<1%]), and skin adverse events (none vs one [<1%]). No grade 4-5 events, brachial plexopathy, serious adverse events, or treatment-related deaths occurred. INTERPRETATION: Hypofractionated postmastectomy radiotherapy provided durable locoregional control with no increase in severe late adverse events compared with conventional fractionation, supporting its use as a more time-efficient option than conventional fractionated radiotherapy. FUNDING: Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, National High Level Hospital Clinical Research Funding, Cooperation Fund of CHCAMS, and CAMS Innovation Fund for Medical Sciences.
Journal of applied clinical medical physicsSuhong Yu, Itai Pashtan
To present a clinical case demonstrating the impact of 4D-CT maximum intensity projection (MIP) reconstruction methodology on internal gross tumor volume (iGTV) definition and to highlight implications for motion management quality assurance. During routine thoracic radiation therapy treatment planning, a discrepancy in tumor extent was identified during physician contouring. The inferior extent of the tumor appeared artificially truncated on the MIP dataset used for target delineation. Further review revealed that the default MIP had been generated from phase-sorted 4D-CT images. A comparison was performed between the phase-sorted MIP and a MIP reconstructed from the original cine images to evaluate differences in motion representation. The phase-sorted MIP under-represented the full tumor motion envelope, most notably in the inferior direction. In contrast, the cine-based MIP demonstrated a more complete representation of tumor extent throughout respiration. This discrepancy was not readily apparent during the routine clinical workflow, and verification of the MIP reconstruction method was not part of the standard QA review process at the time. Differences in MIP reconstruction methodology can impact iGTV definition. Although these differences may be subtle in most cases, clinically meaningful discrepancies may occur, particularly in patients with irregular breathing patterns. This case highlights the importance of awareness and verification of 4D-CT MIP reconstruction methods and supports comprehensive QA across CT simulation, treatment planning, and motion management workflows.
Anticancer researchWon Ick Chang, Bum-Sup Jang, Ji Hyun Chang, Kyubo Kim, Kyung Hwan Shin
BACKGROUND/AIM: The optimal management of close resection margins after breast-conserving surgery (BCS) remains controversial, particularly in hormone receptor-negative (HR-) breast cancer, which has a relatively high risk of local recurrence (LR). This study evaluated the association between resection margin width and LR and identified high-risk factors among patients with close margins. PATIENTS AND METHODS: We retrospectively reviewed 842 patients with HR- breast cancer who underwent BCS followed by adjuvant radiotherapy between 2010 and 2020. Resection margins were categorized as clear (≥2 mm) or close (<2 mm). The cumulative incidence of LR was analyzed using competing-risk methods, and disease-free survival (DFS) was also evaluated. RESULTS: The 10-year cumulative incidences of LR were 4.5% in patients with clear margins and 4.9% in those with close margins, with no significant difference between the groups (p=0.359). In contrast, the 10-year disease-free survival was significantly lower in patients with close margins than in those with clear margins (87.7% vs. 92.2%; p=0.008), and close margins remained independently associated with worse DFS in multivariable analysis (hazard ratio=1.85, 95% confidence interval=1.13-3.05; p=0.015). In the multivariable analysis of patients with close margins who were treated with a tumor bed boost of 0 to 10 Gy, the presence of an extensive intraductal component (p<0.001), a Ki-67 proliferation index ≥15% (p=0.012), and the omission of HER2-targeted therapy or chemotherapy (p=0.010) were significantly associated with an increased cumulative incidence of LR. CONCLUSION: Close margins were not associated with a significantly increased risk of LR in patients with HR- breast cancer treated with contemporary adjuvant therapy, although they were associated with worse DFS. Patients with close margins and additional adverse factors may represent a subgroup in whom intensified local treatment, including a higher tumor bed boost dose, warrants further investigation.