Background Clinician-reported outcomes (CROs) remain a central component of side effect assessment in radiotherapy, while patient-reported outcomes (PROs) are increasingly being integrated into standard practice to better capture the subjective symptom burden experienced by patients. Agreement between CRO and PRO has not been prospectively studied in patients undergoing radiotherapy for brain metastases. Methods NeuroPRO was a prospective longitudinal cohort study enrolling patients receiving radiotherapy for brain metastases. CROs were assessed using predefined CTCAE (version 5.0) items, while PROs were collected using the EORTC QLQ-C30 and BN20 at baseline, end of treatment, and first follow-up. Upon completion of radiotherapy, decision regret was evaluated additionally using the Ottawa Decision Regret Scale. Chance-corrected agreement between CRO and PRO was quantified for each item using Gwet's second-order agreement coefficient (AC2). Longitudinal differences were additionally explored using two-way ANOVA and agreement was further characterized using Bland-Altman analyses with calculation of limits of agreement (LoA). Results Sixty-three patients were included, completing 278 questionnaires and yielding 4448 matched CRO-PRO item comparisons. Across 27 of 32 shared symptoms (84%), PRO scores were higher than CRO scores, indicating systematic symptom underestimation by clinicians. Chance-corrected agreement (Gwet's AC2) was fair to moderate for psychological and neurological symptoms (worry AC2 = 0.30; depression AC2 = 0.39; drowsiness AC2 = 0.44) and substantial to almost perfect for gastrointestinal and treatment-related symptoms (vomiting AC2 = 0.96; seizures AC2 = 0.94; nausea AC2 = 0.92), corroborating the pattern observed with mean-based comparisons. The largest single-item discrepancies were observed for dyspnea (bias 1.00; 95% LoA 0.85–1.14; group p < 0.001), insomnia (bias 0.76; 95% LoA 0.22–1.29; group p < 0.001), and depression (bias 0.75; 95% LoA 0.39–1.12; group p < 0.001). Symptom clustering demonstrated higher agreement for directly treatment-related effects and physical functioning, whereas agreement was substantially lower for emotional and cognitive domains. Patient-reported global health status remained stable after radiotherapy, and decision regret was low. Conclusion Sole clinician assessment systematically underestimates symptom burden in patients undergoing radiotherapy for brain metastases, particularly within psychological domains and somatic symptoms not readily attributable to radiotherapy. These findings reveal a structural perception gap and support the routine integration of PROs into interdisciplinary neuro-oncologic care to enhance symptom recognition and promote patient-centered management (DRKS00031480).
Background With the growing adoption of 5-fraction ultra-hypofractionated radiotherapy (uHFRT) following breast-conserving surgery (BCS), in-treatment breast edema has been increasingly observed. Marked edema may impair target dose coverage and even necessitate radiotherapy interruption. This study aimed to investigate the incidence, evolution and risk factors of this acute adverse event. Methods Patients treated with BCS were enrolled in a prospective phase II trial of uHFRT. Patients received whole-breast irradiation (WBI) at 26 Gy in 5 fractions, with or without simultaneous integrated tumor-bed boost (SIB) of 30 Gy, delivered daily or on alternate days. Cone-beam CT (CBCT) was acquired prior to each fraction. Acute breast edema was defined as outward expansion of the breast contour exceeding 1 mm relative to the planning CT. Clinical and target volume parameters were analyzed to identify risk factors. Results Among 221 patients (224 breasts), edema occurred in 83 breasts (37.1%), with 96.4% developing after the first fraction. The prevalence of edema was 35.7%, 36.6%, 37.1%, and 35.3% at the 2nd to 5th pretreatment CBCT scans, respectively. Edema peaked after the first fraction in 42 swelling breasts (50.6%). Contour expansion was >3–5 mm in 19.6%, >5–8 mm in 7.1%, >8–10 mm in 1.8%, and > 10 mm in 0.9% of all breasts. Multivariate analysis indentified younger age and greater breast thickness as significant factors associated with the occurrence of in-treatment breast edema. Furthermore, breast thickness was positively associated with edema severity. Conclusions The incidence of acute in-treatment breast edema during uHFRT after BCS was 37.1%, with onset immediately after the first fraction in 96.4% of affected cases. Contour expansion >5 mm was observed in 9.8% of the entire cohort. Given the short treatment course and high single-fraction dose, early-onset edema may impair treatment efficacy. Close surveillance and timely intervention are warranted for high-risk patients.
Background and purpose Radiation-induced xerostomia remains a major toxicity after radiotherapy for head and neck cancer (HNC). Although QUANTEC-based parotid dose constraints are widely applied, increasing evidence suggests that additional salivary and oral structures may contribute to xerostomia risk. This systematic review aimed to summarize contemporary evidence on dose-volume predictors of post-radiotherapy xerostomia in HNC. Materials and methods This PRISMA-based systematic review was registered in PROSPERO (CRD42024519338). PubMed, Embase, Cochrane Library, and Web of Science were searched for studies published between January 2013 and August 2025. Studies evaluating dose-volume predictors of xerostomia in adult HNC patients treated with curative-intent radiotherapy were included. Results Fifty-one studies involving 10,789 patients were included. Most patients received intensity-modulated radiotherapy. Contralateral parotid gland mean dose (Dmean) was the most consistently validated predictor of xerostomia and was supported by moderate-certainty evidence. Multiple studies reported increased risk of moderate-to-severe xerostomia when contralateral parotid Dmean exceeded 24–26 Gy, whereas Dmean below 20 Gy was associated with better salivary preservation. Bilateral parotid Dmean around 26 Gy was also reported. However, support for specific numerical planning thresholds remained limited. Dosimetric parameters of the submandibular glands and oral cavity were also independently associated with xerostomia risk. Emerging evidence suggested potential roles of parotid substructures, including ducts and stem cell-rich regions. Conclusion Parotid gland mean dose remains the most robust predictor of post-radiotherapy xerostomia in HNC. Additional dosimetric information from the submandibular glands, oral cavity, and parotid substructures may further improve xerostomia risk stratification and support future NTCP modeling.
Background Older patients with anal squamous cell carcinoma (ASCC) are underrepresented in prospective studies evaluating chemoradiotherapy (CRT). We evaluated patient−/tumor−/treatment characteristics and oncologic outcomes in older patients treated with CRT in a large retrospective multicenter cohort study of the DKTK-ROG. Materials and Methods Patients with localized ASCC treated with CRT between 2004 and 2018, were retrospectively analyzed. Older patients were defined as age ≥ 70 years at CRT initiation. Freedom from recurrence (FFR) and overall survival (OS) were analyzed using Kaplan-Meier estimates, competing-risk analyses, and Cox regression models. Results A total of 683 patients were analyzed, including 180 older patients (≥70 years, 26%). The 3-year FFR and OS rates for the entire cohort were 80.0% (95% CI, 76.9–83.3%) and 87.1% (95% CI 84.5–89.9%), respectively. Competing risk regression for locoregional failure including non complete response or distant metastases with death as competing risk revealed no significant difference between both groups (p = 0.5, p = 0.9, respectively). In contrast, older patients demonstrated inferior OS (p < 0.001). In multivariable analysis, advanced age remained associated with inferior OS (HR 2.51, 95% CI 1.73–3.64, p < 0.001), whereas no association between older age and FFR was observed (HR 1.04, 95% CI 0.69–1.58, p = 0.856); advanced T category and nodal involvement remained the dominant prognostic factors for worse FFR. Interpretation Definitive CRT provides meaningful oncologic control in selected older patients with localized ASCC. Chronological age alone should not preclude curative-intent treatment. Future studies should integrate geriatric assessment to better individualize treatment strategies in older patients.
Background Daily adaptive magnetic resonance (MR)-guided treatment changes delivered dose distributions, making cumulative dose uncertain. This work assessed the feasibility of exploring potential relationships between side effects and accumulated dose (AD) in MR-guided stereotactic ablative radiotherapy (SABR) for liver and pancreatic cancers. Using deformable image registration (DIR), AD to abdominal organs at risk (OARs) were estimated and potential relationships with observed side effects explored. Methods Forty-one patients treated with 5-fraction MR-guided SABR to primary or metastatic pancreatic and liver tumours were retrospectively included. Daily adapted plans were deformably mapped and summed to estimate AD. Differences between accumulated and planned dose were assessed. Changes in clinician-reported symptoms collected at baseline, 3, and 6 months were analysed. Associations between AD and symptoms were assessed using Spearman's rank test. Results Most AD metrics were lower than planned for gastrointestinal OARs, reflecting potential differences from delivered ATS plans, with significant reductions in duodenum and large bowel D0.5cc and D10cc (p < 0.001). Weak associations between small bowel dose metrics and acute and subacute diarrhoea were found (rs 0.4–0.5, p < 0.040). All side effects were ≤ grade (G) 2. Median overall survival for locally advanced pancreatic cancer (LAPC) patients was 16.0 months post-SABR and was not reached for other subgroups. Conclusion Exploring potential relationships between DIR-based accumulated OAR dose and side effects was feasible. Preliminary relationships between accumulated OAR dose and side effects were observed; however, further work in larger studies is warranted before these findings can be used to personalise treatment in the future.
Background and purpose Moderate hypofractionation is increasingly used in salvage radiotherapy (SRT) after radical prostatectomy, although prospective data in the postoperative setting remain limited. We evaluated early adverse events and patient-reported outcomes (PROs) according to fractionation schedule within a prospective multicenter phase III trial. Materials and methods This prespecified interim analysis included the first 250 patients enrolled in the URONCOR 06–24 randomized trial (NCT05781217). SRT was delivered using moderate hypofractionation (n = 175), most commonly 62.5 Gy in 25 fractions (80.5%), followed by 65.25 Gy in 29 fractions (7.5%), 60 Gy in 24 fractions (4.6%), and 52.5 Gy in 20 fractions (2.9%), corresponding to a biologically equivalent dose (EQ.D2) of approximately 65–71 Gy (α/β = 1.5), or conventional fractionation (n = 75; 66–70 Gy in 33–35 fractions). Adverse events were assessed using CTCAE v5.0. PROs were evaluated using EPIC-26 and EORTC QLQ-C30 at baseline, 3, and 6 months. Results With a median follow-up of 12.7 months, grade ≥ 2 genitourinary (GU) adverse events occurred in 21.7% of patients treated with hypofractionation versus 17.3% with conventional fractionation (p = 0.431). Grade ≥ 2 gastrointestinal (GI) adverse events occurred in 10.8% and 4.0%, respectively (p = 0.079). Pelvic nodal irradiation was more frequent in the hypofractionation group (39.4% vs 13.3%, p = 0.001). On multivariable analysis, age was associated with increased risk of GU ≥2 adverse events, while pelvic nodal irradiation was associated with increased risk of GI ≥2 adverse events. No clinically meaningful differences were observed in PROs. Conclusion Early adverse events after SRT were low and comparable between fractionation schedules, and moderate hypofractionation showed a similar safety profile despite more frequent pelvic irradiation. However, given the non-randomized nature of the fractionation schedules, longer follow-up and robust adjustment for treatment-selection biases are needed before drawing definitive conclusions regarding comparative safety.
Purpose Immunotherapy-based total neoadjuvant therapy (iTNT) improves clinical complete response rates and increases organ preservation (OP) opportunities in rectal cancer, while its long-term impacts on quality of life (QoL) and anorectal function remain unclear. This study aimed to evaluate long-term QoL and anorectal function after iTNT, and to clarify how OP versus radical surgery affects patient-reported outcomes and functional recovery, providing evidence for individualized clinical decision-making. Material and methods This prospective longitudinal cohort study enrolled rectal cancer patients receiving iTNT from 2021 to 2024. Patient-reported outcomes were dynamically evaluated using the EORTC QLQ-C30/CR29, Low Anterior Resection Syndrome (LARS), Wexner, and Memorial Sloan Kettering Cancer Center Bowel Function Instrument (MSKCC-BFI) questionnaires. Longitudinal changes were analyzed using linear mixed-effects models accounting for within-patient correlation. A separate conventional TNT cohort was included for exploratory cross-sectional comparison of long-term outcomes. Risk factors for major LARS were evaluated using univariable and multivariable logistic regression with multiple imputation and complete-case sensitivity analyses. Results Of 172 patients receiving iTNT, 142 were eligible for QoL analysis and 137 for anorectal function assessment after excluding five patients with permanent stomas. Patients managed with OP were associated with better global health status, lower symptom burden, and better anorectal function than those undergoing total mesorectal excision (TME), with lower LARS and Wexner scores during follow-up. Compared with conventional TNT, poorer QoL and anorectal outcomes after iTNT were mainly observed in patients undergoing TME, whereas outcomes were largely comparable among those managed with OP. Multivariate analysis identified TME and shorter tumor distance from the anal verge as independent risk factors for major LARS. Conclusion OP following iTNT was associated with more favorable long-term QoL and anorectal functional outcomes than TME. These findings support OP strategies as an important approach for optimizing long-term patient-reported outcomes in appropriately selected patients with rectal cancer.
Postoperative groin lymphatic fistulas are a common complication of vascular surgery and radical lymph node dissection, which may occur in more than 10% of patients. While conservative management remains the standard first-line approach, refractory cases often require invasive interventions. Low-dose radiotherapy has emerged as a potential alternative, despite limited clinical adoption and an incompletely understood mechanism of action. This systematic review evaluates the available evidence on radiotherapy for postoperative groin lymphatic fistulas, focusing on clinical outcomes, safety, and treatment characteristics.A systematic review was conducted in accordance with PRISMA guidelines, searching MEDLINE via PubMed from inception to June 2026. Studies reporting radiotherapy use for postoperative groin lymphatic fistulas in human subjects were eligible. Extracted data included study and patient characteristics, radiotherapy parameters, and clinical outcomes.Twelve retrospective studies published between 1978 and 2026 were included, encompassing 448 patients. Radiotherapy schedules varied in timing (7.5–29 days post-surgery), dose per fraction (0.06–3 Gy), and total prescribed dose (0.5–20 Gy). Most protocols targeted the lymphocele and adjacent tissues, with a median treatment volume of approximately 585 cc. Fistula closure rates ranged from 67% to 100%, with complete response achieved within 5–27 days. Side effects were limited; one study reported a 2.4% incidence of secondary pelvic malignancies potentially attributable to radiotherapy.Radiotherapy appears effective for postoperative groin lymphatic fistulas, achieving high closure rates with low-dose, short-course regimens. However, substantial heterogeneity and the absence of prospective evidence underscore the need for standardized protocols and future prospective studies.
Purpose Incidental pelvic nodal irradiation is an unavoidable consequence of bladder-only radiotherapy (RT) and may contribute to the irradiation of occult microscopic disease. We characterized incidental pelvic nodal dose and compared regional dose distributions between volumetric modulated arc therapy (VMAT) and step-and-shoot intensity-modulated RT (IMRT). Materials and Methods Planning computed tomography datasets from 30 patients receiving bladder-only RT were used to generate paired VMAT and step-and-shoot IMRT plans. Pelvic nodal regions, including the common iliac, external iliac, internal iliac, obturator, and presacral basins, were contoured according to consensus guidelines. Composite and region-specific dose–volume histogram parameters were compared between techniques using paired analyses. Treatment delivery efficiency was evaluated by monitor units (MUs). Results Both techniques achieved equivalent target coverage and comparable incidental pelvic nodal dose distributions. A consistent regional hierarchy of incidental nodal irradiation was observed, with the obturator, external iliac, internal iliac, and common iliac regions receiving approximately 75%, 45%, 25%, and < 5% of the prescribed dose, respectively. These patterns remained remarkably consistent regardless of delivery technique. Although small statistically significant differences were identified for selected regional dose–volume parameters, the magnitude of these differences was generally less than 1 Gy and was considered unlikely to be clinically meaningful. VMAT required significantly fewer MUs than step-and-shoot IMRT (median 914 vs. 1123, p < 0.001). Conclusions Bladder-only RT produces a reproducible regional pattern of incidental pelvic nodal irradiation that is largely independent of delivery technique. The observed consistency across techniques suggests that incidental nodal exposure may be influenced more by target geometry than by the delivery technique.
Purpose Reirradiation has become an area of increasing clinical and scientific interest, particularly in neuro-oncology. This non-systematic review on central nervous system (CNS) tumors by the CNS focus group of the European Society for Radiotherapy and Oncology provides a pragmatic synthesis of the available evidence, excluding gliomas. We address key questions related to patient selection, fractionation, technical considerations, and treatment safety. Methods Relevant studies on the use of reirradiation for meningiomas, ependymomas, brain metastases, and pituitary neuroendocrine tumors, as well as on the management of radiation necrosis, have been reviewed and summarized. Results Reirradiation has been used with varying success in primary and secondary brain tumors. The appropriate use of reirradiation requires consideration of numerous factors, including, but not limited to, prior treatment courses, fractionation, dose to organs at risk, imaging findings, the volume of the recurrent tumor, and the interval since prior treatments. The vast majority of available studies are limited by their retrospective design, lack of standardization in reporting, and overall heterogeneity across cohorts and treatments. Conclusion Several reirradiation studies across different tumor entities suggest potential efficacy and safety in carefully selected patients. However, important limitations remain, underscoring the need for well-designed prospective studies with rigorous reporting in both primary and secondary brain tumors.
Patients treated for head and neck cancer (HNC) receive incidental, non-target radiation to intracranial structures. This prospective study investigated the relationship between regional brain radiation dosimetry and neurocognitive performance during the first year of survivorship. Patients with newly diagnosed HNC completed a comprehensive neuropsychological battery at baseline-prior to or within the first week of radiation therapy, or before induction chemotherapy-(n = 47), and again at 6 months (n = 30) and 12 months (n = 24) after initiating radiation therapy. Cognitive domains assessed included language, learning and memory, and attention, processing speed, and executive function (APE). Deep-learning-assisted contouring was applied to estimate mean radiation doses (Dmean) to eight brain regions. Associations between regional dosimetry and cognitive change were evaluated using Pearson correlation coefficients with 95% confidence intervals (CIs). The highest median Dmean were observed in the cerebellum (430.7 cGy; IQR: 302.3-646.2) and temporal lobes (108.5 cGy; IQR: 72.4-161.2), while the parietal lobe received the lowest (27.5 cGy; IQR: 18.9-39.6). Neurocognitive scores demonstrated modest improvement across domains at both follow-up time points. No significant correlations were identified between region-specific doses and cognitive performance, with most estimates between -0.1 and 0.1. Incidental brain radiation during HNC treatment was not associated with early neurocognitive decline within the first year after diagnosis. This prospective study illustrates the utility of integrating advanced dosimetry with longitudinal cognitive assessments and lays the groundwork for future larger-scale investigations.
Purpose:To identify early post-treatment prostate-specific antigen density (PSA-D) models associated with long-term biochemical recurrence-free survival (bRFS) after ultrahypofractionated prostate radiotherapy without androgen deprivation therapy (ADT), and to compare early kinetic composite models with single post-treatment PSA-D classifiers. Methods and materials:Prospectively collected patients receiving 45 Gy in 5 consecutive fractions without ADT were analyzed. This analysis used a prespecified, clinically driven landmark approach evaluating PSA-D change across early post-treatment intervals while prioritizing interpretability over model complexity. Candidate 2-factor models combined ISUP grade group with PSA-D kinetics in the baseline→3-month and 3 → 6-month windows and were screened by Kaplan-Meier separation, cohort size, and clinical usability, with fixed-time 7-year ROC analysis used descriptively. An exploratory 3-feature composite score was also assessed. Results:The final no-ADT cohort comprised 294 patients with 39 biochemical relapses. Seven-year bRFS was 100.0%, 96.2%, 83.4%, and 73.7% for low-, favorable intermediate-risk (FIR), unfavorable intermediate-risk (UIR), and high-risk disease, respectively. PSA and PSA-D decline rates from baseline to 12 months differed significantly across NCCN risk groups, with steeper declines in UIR and high-risk disease than in FIR disease (both P < 0.001). Relapsing cases showed persistently higher PSA-D trajectories from the earliest post-treatment timepoints, with wider separation by 3 and 6 months. A baseline-anchored model, ISUP ≥3 plus ΔPSA-D(baseline→3 months) >0.138, separated 7-year bRFS at 96.7% versus 62.7% (P < 0.001). The 3 → 6-month model combining ISUP ≥3 plus ΔPSA-D(3 → 6 months) >0.033 separated 7-year bRFS at 93.5% versus 53.4% (P < 0.001). A 3-feature composite score showed the strongest fixed-time discrimination (AUC, 0.772). In Cox analysis, both ISUP ≥3 (HR, 2.26; 95% CI, 1.17-4.40; P = 0.016) and the adverse 3 → 6-month PSA-D term (HR, 3.41; 95% CI, 1.69-6.85; P < 0.001) remained independently associated with biochemical recurrence. Single PSA-D classifiers were predictive but less discriminative. Conclusions:Early PSA-D kinetics may support early risk stratification for long-term bRFS after prostate SABR without ADT. Composite models combining baseline pathologic risk with early PSA-D kinetics provide a treatment-response-based layer of risk stratification that complements baseline NCCN classification. Single PSA-D cutoffs remain informative but are less satisfactory than kinetic models because they do not capture response velocity.
This correspondence comments on the study by Alexander et al. evaluating whether routine rectal preparation is necessary during contemporary image-guided prostate radiotherapy. Although the reported motion differences were clinically small and support reducing burdensome preparation, interpretation is limited by structural differences between treatment schedules, non-equivalent definitions of patient motion, possible clustering of repeated fraction-level measurements, and differing planning rescan thresholds. Enema use was associated with radiotherapy prescription, making direct comparison between preparation groups difficult. Analyses using patient-level summaries or mixed-effects models, adjustment for treatment and anatomical factors, and schedule-normalized outcomes would provide more reliable estimates. The findings are therefore best viewed as supporting risk-adapted deimplementation rather than universal omission of rectal preparation. Prospective regimen-balanced studies incorporating geometric accuracy, delivered dose, toxicity, patient burden, and resource use are needed to determine which patients can safely avoid routine enemas.
This summary statement of the European Lung Cancer Conference (ELCC) 2026 presents an overview of current debates in thoracic oncology from the radiation therapy perspective. A major topic of interest in small cell lung cancer (SCLC) were bispecific T-cell engagers (biTe) in extensive stage carcinomas, especially the use of Tarlatamab. Non-small cell lung cancer (NSCLC) was discussed from the viewpoint of multidisciplinary decision making as investigated in the MDT-Bridge study. Another focus was placed on platform drug-RT trials, such as the CONCORDE study. As for thymomas and thymic cancers, the retrospective evidence available to date was summed up with three ongoing trials for PORT expected to finish recruitment within the next five years. The role of SBRT in oligometastatic disease as local ablative treatment, either as a strategy to delay the shift to the next line of systemic treatment or - upfront - in order to block oligoprogression, was discussed.
Background Radiation oncology workflows generate large volumes of electronic health record (EHR) data requiring daily synthesis. Large language model (LLM)-based automation is promising, but workflow-embedded implementations at scale remain limited. We describe the design and early usability and adoption evaluation of The Daily Dose (TDD), an LLM-driven system for automated clinical summarization and trial identification in radiation oncology. Materials and methods TDD delivers physician-specific email summaries each morning across three Mayo Clinic campuses using RadOnc-GPT (GPT-4o) to generate EHR-derived patient summaries and identify potentially eligible clinical trials for new or consult visits. One month post-deployment, an anonymous cross-sectional survey adapted from the System Usability Scale and Technology Acceptance Model was administered to all recipients. Results Fifty-five of 110 users responded (50%); 94.5% were in radiation oncology and 69.1% were attending physicians. Overall, 83.6% used TDD at least several times per week. Mean domain scores (5-point Likert) were 3.89 ± 1.04 for usability and satisfaction, 3.43 ± 1.24 for perceived usefulness, and 3.80 ± 1.17 for impact and future use. Satisfaction was significantly associated with perceived time savings (p < 0.001); 27% estimated saving ≥10 min daily. Internal consistency was high (α = 0.97). Free-text responses highlighted improved preparedness and patient-context awareness but noted occasional inaccuracies and imperfect trial matching. Conclusion In this early usability and adoption evaluation, a workflow-integrated LLM summarization tool was widely adopted and generally favorably perceived. These findings reflect user perceptions; objective validation of summary accuracy, trial-matching performance, and workflow efficiency is needed to establish clinical impact.
Purpose:Bulky advanced hepatocellular carcinoma (HCC) remains difficult to treat with conventional homogeneous ablative radiotherapy because safe dose escalation is limited by hepatic reserve, tumor-to-liver geometry, and adjacent organs at risk (OARs). This study evaluated local control, tumor response, toxicity, and treatment continuity after volumetric-modulated arc therapy (VMAT)-based lattice radiotherapy (VMAT-LRT) in patients with advanced HCC. Methods:We retrospectively reviewed our initial consecutive VMAT-LRT cohort treated between October 2024 and March 2026. VMAT-LRT was considered for tumors >300 cm3 or unfavorable tumor-to-liver or tumor-to-OAR geometry that rendered SBRT or homogeneous curative-dose radiotherapy unfeasible, while local treatment remained indicated. VMAT-LRT delivered high-dose intratumoral lattice spheres using VMAT-based planning, followed by lower-dose peripheral irradiation individualized according to clinical goals. Endpoints included local control, tumor response, RILD, CTCAE toxicity, and treatment continuity. Results:Twelve VMAT-LRT courses in 11 patients were completed as planned. Median age was 70 years, median follow-up was 6.1 months, and median initial tumor volume was 557 cm3. Objective tumor response was observed in all treated courses. Median relative and absolute volume reductions were 65% and 320 cm3, respectively. Local control was achieved in all courses, with no documented local progression. Four patients achieved complete response. Systemic or subsequent anticancer therapy continued after radiotherapy in 8 of 11 patients without interruption attributable to acute radiotherapy-related toxicity. Acute toxicity was limited to Grade 0-2 events. RILD was Grade 0 in 10 evaluable courses and Grade 3 in one course. No late toxicity was recorded among 11 evaluable courses. Conclusion:VMAT-LRT was feasible for advanced bulky HCC, achieving meaningful tumor regression and durable in-field local control with acceptable toxicity while allowing continuation of multimodality treatment in selected patients.
Background:The Notch signalling pathway regulates cell fate, proliferation, and differentiation and consists of receptors (Notch1-4), ligands (JAG1-2, DLL1, DLL3-4), and downstream targets. Altered expression of Notch pathway-linked genes has been reported in multiple cancers, although their associations with survival may vary according to tumour type. Their relationship with biological sex and radiotherapy (RT) has been less extensively explored. Purpose:To explore associations between Notch pathway-linked gene expression and overall survival (OS) across multiple cancer types, and to examine whether these associations differ by biological sex or in an RT-treated lung cancer subgroup. Methodology:Gene expression and clinical data from patients across nine cancer types were analysed using publicly available datasets derived from The Cancer Genome Atlas (TCGA) and the Kaplan-Meier Plotter platform. Associations between the expression of 14 Notch pathway-linked genes and OS were evaluated using Kaplan-Meier survival analyses. Representative findings were further evaluated using multivariable Cox proportional hazards models incorporating clinical covariates and gene expression × sex interaction terms. Main findings:Across nine cancer types, 13 of the 14 Notch pathway-linked genes were significantly associated with OS in at least one tumour type. DLL3 and JAG1 demonstrated recurrent associations across multiple cancers, with higher DLL3 expression more frequently associated with poorer OS. Sex-stratified analyses identified additional prognostic associations; however, multivariable interaction analyses did not consistently support biological sex as an effect modifier. In the RT-treated lung adenocarcinoma subgroup, higher JAG1 expression was associated with poorer OS, although this association was not confirmed in an adjusted pan-cancer RT validation cohort. Conclusion:This exploratory pan-cancer analysis identified associations between the expression of several Notch pathway-linked genes and OS, including recurrent associations involving DLL3 and JAG1. Differences observed in sex-stratified analyses and the RT-treated lung adenocarcinoma subgroup warrant further investigation in independent cohorts.
Objective:Submandibular gland (SMG) transfer to the submental space in patients undergoing head and neck radiation therapy was historically performed to decrease radiation-associated xerostomia in the era of 2D/3D radiotherapy. In this study, we evaluated the dosimetric significance of SMG transfer with intensity modulated proton therapy (IMPT). Methods:We reviewed patients with oropharyngeal carcinoma who received curative intent definitive radiation and had contralateral (C/L) SMG transfer. We registered the baseline diagnostic computed tomography (CT) scan of these patients with the CT simulation images and delineated pre-transfer and post-transfer SMG locations. IMPT pre-transfer plans were generated, taking into consideration the initial reference SMG position, and then re-optimized based on the post-transfer SMG position. Each patients' dosimetric parameters from both plans were compared for mean SMG doses, target coverage and other OAR doses. Results:Seventeen patients were included in the analysis. All patients received definitive radiation (66-70 Gy/30-35 fractions). Pre-transfer plans had a C/L SMG mean dose of 32.92 Gy (range [R]: 17.82-47.6 Gy), which decreased to 20.22 Gy (R: 9.75-38.87 Gy), p < 0.001 on re-optimization. Post-transfer plans met the mean dose constraints more often than pre-transfer plans. The difference in C/L SMG mean dose with gland transfer was 12.02 Gy (95% CI: 9.46-14.59 Gy; p < 0.001). There was no significant difference in target coverage, ipsilateral SMG, and any other OARs between the plans. Conclusion:This pilot study demonstrates that SMG transfer enables better C/L SMG dose sparing during IMPT. Future prospective studies with larger patient cohorts are warranted to support clinical translation.
Purpose:Radiation dose reduction to major memory circuit substructures (e.g., hippocampus, amygdala, fornix, and corpus callosum) may reduce patients' neurocognitive toxicities. We evaluated memory circuit (MC) dosimetry and determined the feasibility of the "Sparing Memory with Advanced Radiosurgery Targeting" (SMART) technique in patients with brain metastases. Materials and methods:Retrospective contouring of MC substructures was performed for 101 patients that received single-fraction, linear accelerator (LINAC)-based, monoisocentric SRS plans for increasing numbers of brain metastases: 1, 2-4, 5-9 and ≥ 10. Patients with ≥10 lesions (n = 13) were reoptimized using SMART by maximizing dose reduction to MC while maintaining >95% PTV coverage (V100% > 95%). Dosimetric parameters such as Dmean, Dmax, and Dmedian to MC, cumulative PTV and MC volume were evaluated. Results:Patients with ≥10 brain metastases received significantly higher Dmean (2.9 vs. 0.41 Gy, p < 0.0001), Dmedian (2.9 vs. 0.34 Gy, p < 0.0001) and Dmax (9.0 vs. 1.9 Gy, p < 0.0001) to the MC compared to those with a single metastasis. SMART replanning yielded a significant decrease in Dmean, Dmedian, Dmax, and D100 doses to the MC when compared to clinical dosimetry (2.9 vs. 1.8 Gy, p = 0.0001; 2.9 vs. 1.8 Gy, p = 0.0002; 9.0 vs. 4.7 Gy, p = 0.0007; 1.5 vs. 0.98 Gy, p = 0.0010, respectively). Conclusion:Increased number of brain metastases results in higher MC doses. Patients with ≥10 lesions received increased Dmean/Dmedian/Dmax doses to the MC compared to patients with <10 brain metastases. SMART technique is clinically feasible. Studies evaluating the neurocognitive benefits of SMART are warranted.
