Abstract Background Concurrent cisplatin and radiotherapy frequently cause severe acute hematologic toxicity. This study investigated whether lymphocyte apoptosis, quantified via the γ-H2AX pan-nuclear immunostaining assay, can serve as a reliable biomarker for the acute hematologic side effects of combined chemoradiation. Methods Blood samples were collected from cancer patients and healthy controls. Lymphocyte apoptosis was evaluated using the γ-H2AX pan-nuclear assay following in vitro and in vivo exposure to cisplatin and ionizing radiation (IR). In PBMCs, γ-H2AX results strongly correlated with conventional caspase-3 (r = 0.9736) and annexin V (r = 0.9780) apoptosis assays. Additionally, in vitro experiments assessed how phytohemagglutinin-L (PHA-L)-induced lymphocyte proliferation influences the combined effects of cisplatin and IR on apoptosis, alongside the regulatory role of the ATM protein. Results In vitro, cisplatin increased lymphocyte apoptosis asymptotically, plateauing at 10 µg/ml (11.6 ± 5.0%). Combined cisplatin and IR treatment increased apoptosis in a strictly additive manner (radiation effect: p < 0.0001), with no significant synergistic interaction effect between the two modalities (p = 0.22). The apoptotic effect level of in vivo cisplatin administration did not differ significantly from the maximum effect observed following a 1-hour in vitro exposure to high cisplatin concentrations. In vivo, the additive effect of cisplatin on IR-induced apoptosis peaked up to 3 days post-administration before returning to baseline by day 6. Consistent with these findings, cisplatin and radiation induced a significant, additive increase in apoptosis within PHA-L-stimulated lymphocytes. Inhibition of ATM has no effect on apoptosis following treatment with cisplatin and IR. Conclusions The γ-H2AX pan-nuclear assay provides a valid, reliable method for quantifying radiation- and chemotherapy-induced lymphocyte damage. The time-dependent, additive toxicity observed indicates a critical clinical window (up to 3 days post-cisplatin) for maximum hematologic damage, allowing for optimization of treatment schedules. Clinical trial number Not applicable.
Abstract Purpose Deep inspiration breath hold (DIBH) is widely used to reduce cardiac dose in left-sided breast radiotherapy. However, the reliability of DIBH at CT simulation, has not been systematically evaluated despite the importance of CT simulation as the basis for treatment planning. We investigated the clinical impact of surface-guided breathing training on DIBH reliability and cardiac dose sparing. Methods In this retrospective cohort study, 115 breast cancer patients undergoing DIBH CT simulation were analyzed before and after implementation of surface-guided breathing training using an SGRT system. DIBH performance was quantified by partial lung volume increase (PLVI) and breath-hold variability. Correlations between external surface motion and internal DIBH depth were assessed. Cardiac dose metrics were compared, with a subgroup analysis for patients receiving lymphatic drainage area (LDA) irradiation. Results Prior to training, insufficient DIBH CTs—including negative PLVI cases—were observed. After training implementation, all CT scans were acquired in intended breath-hold states, eliminating insufficient DIBH acquisitions. Mean PLVI increased by ~ 9%, and breath-hold variability decreased by ~ 26%. Sternum motion correlated most strongly with PLVI, with multiregion surface monitoring yielding the highest internal correlation. These improvements were reflected in significant reductions in cardiac dose, particularly in the LDA subgroup, with selected heart dose metrics reduced up to 96%, while maintaining target coverage. Conclusions DIBH at CT simulation with surface-guided breathing training proves to be reliable. The training prevents planning CTs in wrong breathing states and thus enables clinically meaningful cardiac dose reduction in breast radiotherapy.
Abstract Background Deep inspiration breath-hold (DIBH) is a radiotherapy standard technique for cardiac-sparing in breast cancer, particularly for left-sided tumors. However, not all patients can successfully complete DIBH RT in clinical routine, necessitating conversion to free breathing (FB) techniques and replanning. This study aimed to identify clinical factors predictive of DIBH feasibility to optimize patient selection and resource utilization. Methods This retrospective study analyzed all patients ( n = 1920) who underwent curative postoperative breast cancer radiotherapy at our institution between May 2020 and December 2024. All patients underwent initial DIBH feasibility assessment and were evaluated for completion of radiotherapy with DIBH or conversion to FB technique. A detailed subanalysis was performed for all patients treated in 2023 ( n = 470). Patient-related factors including age, body mass index (BMI), Karnofsky Performance Status (KPS), Charlson Comorbidity Index (CCI), pulmonary comorbidities, smoking status, and geometric surface distance between DIBH and FB planning scans were collected for the subanalysis. Results Across the entire cohort (years 2020–2024) of 1,920 patients, 78 replannings (4%) occurred due to conversion from DIBH to free breathing. Increasing age (cut-off of 63 years) was significantly associated with higher replanning rates ( p = 0.001). In the 2023 subanalysis ( n = 470), pulmonary comorbidities ( p = 0.008), higher CCI ( p = 0.044), and a geometric surface distance of below 1 cm between DIBH and FB CT scans ( p = 0.0001) were significant predictors of replanning. The Karnofsky Performance Score, BMI, and smoking status showed no significant association with replanning. Conclusions Age, pulmonary comorbidities, overall comorbidity burden, and insufficient geometric displacement are significant predictors of DIBH failure in breast cancer radiotherapy. These readily available clinical parameters can optimize patient selection algorithms and inform decisions regarding dual CT simulation workflows. A risk-stratified approach incorporating these factors may reduce unnecessary imaging, decrease planning burden, and improve resource allocation while maintaining optimal cardiac protection for appropriate candidates. Clinical trial number The study was registered in the German Clinical Trials Register (DRKS; registration number: DRKS00038550) on 22 December 2025 ( https://www.drks.de/ ).
The sparing effect of FLASH irradiation with ultrahigh dose rates (UHDR), by applying high dose fractions in less than one second, on adverse reaction in many normal tissues but not on tumour control has the potential to widen the therapeutic window and advance cancer radiotherapy. However, the mechanism is poorly understood, preventing its optimal application in the clinic. Here we review the current knowledge of radiation-induced radicals and their reactions, including time factors which are rarely considered. Furthermore, experimental in vitro and in vivo data in the framework of prevailing hypotheses, and the role of low oxygen concentrations and reoxygenation, are discussed. Finally, potential protective mechanisms are considered based on such reactions and the role of oxygen. We argue that more than one mechanism may contribute to dose-rate dependent protection, and that differences exist between protective mechanisms in vitro and in vivo. Furthermore, we propose a new protective reaction linking radiation chemistry to the role of oxygen in FLASH irradiation and incorporating the differential responses of normal tissue and tumours.
The ZAP-X® Gyroscopic Radiosurgery® platform (ZAP Surgical Systems, Inc., San Carlos, CA, USA) is a novel self-shielded image-guided radiotherapy device developed for frameless stereotactic radiosurgery (SRS) and fractionated SRS (FSRS) of intracranial and cervical spine lesions. This article presents technical aspects and dosimetric results for SRS and FSRS using the ZAP-X system for meningioma patients. Unique technical aspects of our treatment workflow using the ZAP-X system encompassing computed tomography simulation, treatment planning, independent dose calculations, patient-specific quality assurance (PSQA) and treatment delivery were described. Eighteen single-lesion meningioma patients, who were treated following this workflow, were selected and divided into two groups (Group A [thirteen patients]: 25 Gy in 5 fractions, FSRS); Group B [five patients]: 15 Gy in a single fraction, SRS). Plan quality metrics, independent dose calculations and PSQA for each group were reviewed and analyzed. For Group A, mean age (range) was 60 years (35 years − 80 years) and mean planning target volume (PTV) (range) was 4.78 cc (2.10 cc − 9.38 cc). Mean (range) PTV coverage, prescribed isodose line, Paddick conformity index, gradient index, number of isocenters, number of beams, delivery time estimate per fraction and PSQA gamma passing rate were 99.5
For locally advanced rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) combined with total mesorectal excision has emerged as the standard therapeutic approach, as delineated in contemporary clinical guidelines. Pathological complete response (pCR) serves as a pivotal metric for assessing nCRT efficacy, with strong correlations to long-term survival outcomes and organ preservation strategies such as the “watch-and-wait” approach. However, inter-individual variability in treatment responses results in only approximately 20
Breast cancer radiotherapy and autoimmune myositis intersect in a clinically complex setting in which paraneoplastic disease, pre-existing inflammatory myopathy, and radiation-related muscle injury may overlap. Dermatomyositis is the idiopathic inflammatory myopathy most strongly associated with malignancy, and breast cancer is one of the solid tumours most frequently reported in cancer-associated myositis, particularly in anti-TIF1γ- and anti-NXP2-positive subsets. A structured narrative review of PubMed and Scopus was performed from database inception to March 2026. Evidence was synthesised qualitatively owing to limited and heterogeneous literature. Muscle symptoms during breast cancer treatment may reflect autoimmune, paraneoplastic, radiation-induced, fibrosis-related, or recall myositis. MRI is the most informative modality for pattern-based assessment, with FDG PET-CT and ultrasound providing complementary value in selected cases. Although direct disease-specific evidence is sparse and derives largely from retrospective series, mixed connective tissue disease cohorts, radiobiological studies, and case reports, radiotherapy does not appear to represent an automatic contraindication when disease activity, multidisciplinary evaluation, and conformal planning are taken into account. Breast cancer radiotherapy in patients with autoimmune or cancer-associated myositis requires structured differential diagnosis rather than categorical avoidance. Diagnostic assessment should integrate timing, field distribution, imaging, serology, systemic features, and treatment sequence. Further studies should refine risk stratification, muscle-specific dose constraints, and biomarkers distinguishing radiation-related from autoimmune or paraneoplastic myositis.
Radiation-induced endothelial dysfunction is a critical mechanism underlying long-term cardiovascular and multiorgan toxicity in cancer survivors after radiotherapy. This review integrates current evidence on the molecular pathogenesis, from initial endothelial apoptosis and senescence to the establishment of chronic pro-thrombotic and pro-inflammatory phenotypes involving various signalling pathways. Clinical data reveal that even low to moderate radiation doses can cause sustained endothelial injury, contributing not only to vascular diseases but also to common cerebrovascular and gastrointestinal complications. Advances in vascular imaging and circulating biomarkers facilitate earlier detection of subclinical damage. Promising protective strategies include statins, angiotensin-converting enzyme inhibitors, and pathway-targeted agents. Future research directions include the development of advanced preclinical models and the conduct of large-scale, prospective clinical studies to validate biomarkers and therapeutic interventions, ultimately aiming to integrate vascular preservation into personalized radiotherapy strategies.
In patients with lumpectomy for left-sided early breast cancer, whole breast irradiation (WBI) in prone position (PP) is an acceptable alternative to WBI in supine position (SP). We compared the less well explored right-sided PP WBI with SP WBI to identify the optimal organ at risk protection. We retrospectively analyzed WBI-plans for 30 patients with right-sided early breast cancer in PP and SP. SP-plans were created with intensity-modulated radiotherapy (IMRT) and deep inspiratory breath hold (DIBH); PP-plans with 3D conformal radiotherapy and free breathing (FB). For better comparison of the different positioning, we additionally calculated IMRT-plans in PP and FB. We compared the extent of the clinical and planning target volumes (CTV and PTV) and the radiotherapy doses applied to CTV, PTV, right lung, heart, coronary arteries, left breast, and the right-sided axillary levels. Furthermore, we analyzed the possible impact of the breast size on the doses applied to the heart and right lung. Compared to SP, PP WBI was associated with lower doses applied to the right lung (Dmean right lung SP 5.6 Gy vs. 3.5 Gy PP, p < 0.001) but higher doses to the heart (Dmean heart SP 0.4 Gy vs. 0.7 Gy PP, p < 0.001) and coronary arteries, and a diminished dose coverage of the target volumes (V95PTV PP 90.4
The optimal postoperative adjuvant treatment for pathological T3N0M0 (pT3N0M0) thoracic esophageal squamous cell carcinoma (TESCC) remains unclear. This study evaluated whether adding radiotherapy to postoperative chemotherapy provides an additional survival benefit in these patients. We retrospectively reviewed 1,090 TESCC patients treated at Sichuan Cancer Hospital (2009–2020). After applying inclusion and exclusion criteria, 356 patients who received adjuvant therapy were analyzed: 274 underwent surgery plus postoperative chemotherapy (S+POCT) and 82 received surgery plus postoperative chemoradiotherapy (S+POCRT). Propensity score matching balanced baseline characteristics between groups. Overall survival (OS) and disease-free survival (DFS) were compared, and survival predictors were assessed using a Cox proportional hazards model. Before matching, the S+POCRT group had more female patients, and patients with vascular or perineural invasion were more likely to receive chemoradiotherapy. After matching (82 patients per group), baseline characteristics were balanced. The 5-year OS was 70.9
In intensity-modulated proton therapy (IMPT), the benefit of adding planning organ-at-risk volume (PRV)-like nominal constraints to direct robust optimization for serial organs at risk remains uncertain when target-OAR separation is minimal. Using paraspinal chordoma as a model, we evaluated whether an additional nominal canal/thecal sac (PRV-like) constraint improves OAR sparing or compromises target coverage. Ten patients with paraspinal chordomas were planned using two IMPT strategies: direct cord robust optimization alone (Cord-RO) and direct cord optimization with additional nominal canal/thecal sac constraint (Canal-RO). PTV-based helical tomotherapy (HT) was generated as a secondary benchmark. Prespecified institutional criteria were used for planning, prioritizing OAR constraints over coverage; when standard coverage goals were not achieved, GTV D98 ≥ 59 Gy(RBE) was accepted as the fallback criterion. Endpoints included target coverage, cord/canal doses, and robustness. Statistical comparisons used Wilcoxon signed-rank, Friedman, and Cochran’s Q tests, two-sided, p < 0.05. All plans met plan-specific OAR constraints. Cord-RO achieved superior target coverage (median HR-CTV D98 [Gy(RBE)]: 63.05 vs. 57.38 vs. 59.46; p ≤ 0.002) and met the fallback objective (GTV D98 ≥59 Gy[RBE]) in 10/10 cases versus 4/10 and 7/10 (p=0.011) in Canal-RO and HT respectively. Robustness favored Cord-RO (median worst-case CTV D95: 90
Stereotactic arrhythmia radioablation (STAR) is an emerging treatment for refractory or recurrent arrhythmias. Compared with conventional stereotactic body radiotherapy (SBRT), STAR involves greater complexity in target delineation, motion management, and organs at risk (OARs) protection, yet it lacks established consensus clinical guidelines, and workflow-specific risk analyses remain limited. To develop a C-arm linear accelerator (LINAC)-based STAR workflow and perform a failure modes and effects analysis (FMEA) with fault tree analysis (FTA), supplemented by an exploratory segment-based anatomical proximity analysis. A multidisciplinary team constructed a process map for C-arm LINAC-based STAR and identified potential failure modes across the workflow. Risks were scored using occurrence, severity, and detectability to calculate risk priority numbers (RPNs), and FTA was used to analyze causal pathways. In a predefined exploratory imaging subgroup of eight patients with ventricular tachycardia and simulation-acquired coronary computed tomography angiography (CCTA), we divided the left ventricle according to the 17-segment model and measured the minimum distances from each segment to adjacent OARs as an anatomical surrogate of exposure likelihood. Seventy-nine failure modes were identified, of which 17 were classified as high risk. The highest-risk failure modes were concentrated in target delineation and motion-related steps, including inaccurate multimodal image registration (RPN 432), improper motion evaluation/management (RPN 336), and diagnostic error of arrhythmia substrate definition (RPN 320). In the exploratory imaging subgroup (n = 8), segmental spatial patterns were moderately consistent across patients, with most standard deviations of minimum distance below 2.0 cm, although variability remained for several segment-OAR relationships. Segments 4, 5, and 10 were each located within 2 cm of both the stomach and esophagus, indicating relatively higher anatomical proximity-related risk. In this FMEA of C-arm LINAC-based STAR, the principal high-risk workflow steps were concentrated in substrate definition, image registration, and motion management. The segment-based analysis provides an exploratory anatomical risk-mapping framework for OAR awareness. Further multicenter studies are needed to refine workflow risk prioritization and evaluate the clinical relevance of the segment-based anatomical findings. Not applicable.
Acute radiation-induced esophagitis (ARIE) remains a clinically significant toxicity during definitive thoracic radiation therapy (TRT), particularly in patients with close esophagus–planning target volume (PTV) proximity. This study evaluated a risk-adapted, dose-optimized esophagus-sparing (ES) strategy designed to reduce ARIE while maintaining adequate target coverage in high-risk patients. Eighty patients with lung cancer treated with definitive TRT between May 2023 and January 2025 were enrolled. The injury-effective esophagus (IEE) was defined as the local high-risk esophageal segment consisting of the central-IEE and an additional 2-cm superior and inferior cranio-caudal expansion. The central-IEE encompassed all axial levels where PTV–esophagus overlap was present, and the ES region was contoured as the portion of the IEE outside the PTV. Based on the degree of PTV/central-IEE overlap (< 1/3, 1/3–2/3, > 2/3), the ES mean dose was constrained to 1/3, 1/2, and 2/3 of the prescribed dose, respectively. ARIE was graded using Radiation Therapy Oncology Group (RTOG) criteria. Progression-free survival (PFS) was defined from initiation of the TRT to progression or death; overall survival (OS) was also evaluated. Among 80 high-risk patients with the esophagus located within 5 mm of the clinical target volume (CTV), ARIE occurred in 24 patients (30.0
Precise spatial distribution of interstitial needles is critical for 3D-printing-assisted brachytherapy in cervical cancer. This study proposes a greedy algorithm-based needle trajectory planning (GANTP) framework to generate patient-specific needle configurations while ensuring needle collision avoidance and achieving clinically acceptable high-risk clinical target volume (HR-CTV) coverage in compliance with OAR dose constraints. The GANTP framework comprises three core steps: (1) Generation of candidate trajectories anchored within clinically viable entry zones; (2) Parameter-driven greedy selection of needle trajectories based on a geometric influence radius (δ) evaluated at three discrete values (12, 15, and 18 mm), where δ serves as a geometric surrogate for dose coverage, together with a geometric coverage-ratio threshold (γ = 98
Radiotherapy (RT) for treating breast cancer can result in incidental dose deposition to the liver, leading to functional impairment. FLASH radiotherapy (FLASH-RT), delivered at ultra-high dose rates (UHDR), has demonstrated remarkable normal tissue sparing. We investigated the hepatoprotective effects and metabolic alterations associated with FLASH-RT and conventional radiotherapy (CONV-RT) in a preclinical breast cancer model. Female BALB/c mice bearing syngeneic 4T1 breast tumors were randomized to receive a single 20 Gy fraction of either FLASH-RT (625 Gy/s) or CONV-RT (0.54 Gy/s) using a 6 MeV electron beam. Tumor kinetics and systemic toxicity were monitored for 14 days. Hepatic integrity was assessed via histology, immunohistochemistry, oxidative-stress markers, serum biochemical assays, and non-targeted UPLC-MS/MS metabolomics of liver tissue. Both modalities achieved isoeffective tumor growth delay. However, FLASH-RT induced only transient body-weight reduction followed by rapid recovery, and was associated with reduced hepatic injury markers compared with CONV-RT. Histopathological analysis revealed that FLASH-RT preserved hepatic architecture and attenuated early pro-fibrotic signaling, as reflected by reduced α-SMA and Nestin expression compared with CONV-RT. FLASH-treated mice exhibited significantly lower serum ALT/ALP levels and reduced oxidative stress (lower MDA levels and higher GSH-PX levels). Furthermore, FLASH-RT attenuated immune-mediated inflammation, as evidenced by diminished infiltration of CD8 + T cells and F4/80 + macrophages. Metabolomic profiling demonstrated that FLASH-RT preserved hepatic metabolic homeostasis, preventing the profound lipid and choline metabolism disruptions observed following CONV-RT. FLASH-RT was associated with substantial hepatic sparing by preserving structural integrity, attenuating oxidative–inflammatory signaling, and maintaining metabolic stability. These findings suggest that FLASH-RT may help expand the therapeutic window by uncoupling antitumor efficacy from collateral hepatic toxicity.
Radiotherapy (RT) for localized gastric lymphoma requires large margins due to respiratory motion. Breath-hold RT is performed to reduce respiratory motion. However, intrafractional variation (IV) during breath-hold RT has not been fully evaluated. We quantitatively evaluated IV during breath-hold RT for gastric lymphoma. Twenty-one patients with localized gastric lymphoma underwent breath-hold RT between 2013 and 2023. They underwent 3–4 computed tomography (CT) simulation scans with breath-holding during the end-expiratory phase of the respiratory cycle. Two radiation oncologists jointly defined a clinical target volume (CTV), and the sum of all CTVs (CTVsum) was defined as the volume covering the CTVs of all CT images. We evaluated CTV changes, displacement of the CTV center, and displacement of each CTV border from the CTVsum. The maximum displacement of the initial breath-hold CT scan (CT1) from the CTVsum was compared with the mean of subsequent breath-hold CT scans (CT2–4) in each direction (anterior–posterior [AP], left–right [LR], superior–inferior [SI]) and across all directions (overall). Factors influencing the maximum overall displacement were assessed using the Mann–Whitney U test (p < 0.05). Mean CTV was 209 ± 86 cm³, with all patients showing maximum volumetric changes within 4
To evaluate the efficacy and safety of neoadjuvant chemoradiotherapy plus immune checkpoint inhibitors (CRT-ICI) for mismatch repair proficient (pMMR) locally advanced rectal cancer (LARC). Five databases were systematically searched. Pooled pathological complete response (pCR) and composite clinical response (CR) and grade 3–4 neoadjuvant-related adverse events (AEs), surgical AEs, and immune-related AEs (ir-AEs) were calculated, and comparative results (CRT-ICI vs. CRT alone) were conducted on randomized clinical trials (RCTs) via risk ratios (RRs). Also, subgroup analyses were conducted in pMMR-exclusive cohorts for all available endpoints. Eighteen studies (1,619 patients) were included. The pooled pCR rate was 41
The clinical value of induction chemotherapy (IC) in stage III-IV oropharyngeal squamous cell carcinoma (OPSCC) remains controversial. While randomized trials have shown limited survival benefit in unselected populations, it remains unclear whether IC provides benefit in high-risk subgroups and whether early treatment response to IC can serve as a prognostic and stratification tool. We conducted a two-center retrospective real-world cohort study of 496 patients with stage III-IV OPSCC treated with definitive radiotherapy with or without IC. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics, adjusting for age, sex, smoking, alcohol use, T/N stage (AJCC 7th), tumor subsite, HPV status, clinical extranodal extension (cENE), and use of concurrent chemoradiotherapy. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) were compared using Kaplan-Meier and Cox proportional hazards models. A clinical nomogram was developed to predict individual DMFS and estimate IC benefit. In IC-treated patients, analyses were stratified by HPV status and IC response further stratified prognosis across endpoints. In IPTW-weighted multivariable Cox analysis, IC was independently associated with improved DMFS (HR = 0.60, 95
PURPOSE:Stereotactic body radiation therapy (SBRT) is widely used for pulmonary oligometastatic disease. Guideline-based regimens target a biologically effective dose [Formula: see text]; However, this threshold may not be achievable in patients with limited physiological reserve or ultracentral lesions. We examined outcomes after SBRT with [Formula: see text] versus [Formula: see text] in a consecutive cohort of patients with recurrent lung-only metastases. METHODS AND MATERIALS:Consecutive patients treated with SBRT for recurrent lung-only metastases between January 2019 and December 2022 were retrospectively reviewed. Primary endpoints were overall survival (OS), progression-free survival (PFS), and freedom from local-regional progression (FFLP). Kaplan-Meier estimates were compared using log-rank tests, and univariable Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). A propensity-score inverse probability of treatment weighting (IPTW) analysis adjusted for age, Eastern Cooperative Oncology Group (ECOG) performance status, Charlson Comorbidity Index (CCI), lung primary status, and number of metastases. RESULTS:Fifty-three patients were included. Median OS was 47.3 months for [Formula: see text] versus 34.3 months for [Formula: see text] (HR 1.45; 95% CI 0.66-3.16; [Formula: see text]). Median PFS was 22.8 months versus 14.7 months (HR 1.59; 95% CI 0.82-3.11; [Formula: see text]). For FFLP, the HR was 2.67 (95% CI 0.60-11.93; [Formula: see text]). In IPTW-weighted models, [Formula: see text] was not significantly associated with OS (HR 0.58; 95% CI 0.25-1.32; [Formula: see text]) or PFS (HR 0.59; 95% CI 0.24-1.40; [Formula: see text]). CONCLUSION:In this retrospective cohort, [Formula: see text] was delivered to selected higher-risk patients on the basis of frailty, ultracentral anatomy, or both. Differences in OS, PFS, and FFLP compared with [Formula: see text] did not reach statistical significance, and IPTW-weighted estimates were directionally consistent. These observations are consistent with the feasibility of sub-ablative SBRT in selected higher-risk patients when ablative dosing is not safely deliverable, and they define the patient population and dose parameters that warrant prospective, risk-stratified evaluation.
To predict tumor micro-infiltration (TMI) within glioblastoma (GBM) peritumoral edema (PTE) using MRI for postoperative radiation planning. Study cohort consisted of a training group (TG) with 50 GBM and 50 brain metastasis tumor cases, a validation group (VG) with 25 GBM and 19 meningioma cases, and an image-pathology point-to-point VG (IPVG) with 10 additional GBM cases. Besides univariate analysis of gray-level histogram parameters (GLHP) of peritumoral edema (PTE) from contrast-enhanced T1-weighted imaging (CE-T1WI), T2 fluid-attenuated inversion recovery (T2FLAIR), and apparent diffusion coefficient (ADC) maps, LASSO regression removed collinear parameters. Then, forward stepwise logistic regression, SVM, and random forest were used to build TMI prediction models in PTE, with efficiency evaluated via ROC curves. In the IPVG, the coincidence rate between Python-based TMI predictions and biopsy pathology results was calculated. Univariate analysis in the TG revealed that GLHP differences between GBM and BM PTE belts were prominent within 3 cm of PTE. After removing collinear parameters, the ADC map or CE-T1WI-based prediction model outperformed the T2FLAIR-based one. The model with the 1-cm GBM PTE belt and 2-cm BM PTE belt pairing showed superior discrimination. Incorporating ADC and CE-T1WI parameters, the RF model with 6 parameters (Ratio-maxi-enhancedT1/mean-enhancedT1, Ratio-miniADC/meanADC, etc.) demonstrated the best discrimination than other models, with an ROC curve (AUC) of 0.836 in the TG and 0.844 in the VG. In the IPVG, the TMI prediction model had an overall accuracy of 81.25
