Stage I-III limited-stage small cell lung cancer (SCLC) is a highly aggressive yet potentially curable disease with concurrent chemoradiotherapy. Thoracic radiation therapy (RT) plays a central role in the management of stage I-III SCLC; however significant variation exists in staging, target volume delineation, dose prescription, and integration with systemic therapy. This document provides an updated European recommendations on the use of RT in stage I-III SCLC, reflecting recent evidence and advancements in clinical practice. A panel of European experts was convened under the auspices of the ESTRO Guidelines Committee, in collaboration with EORTC Lung Cancer Group, and to review the available evidence and develop recommendations. Key topics addressed included disease staging, radiotherapy planning and delivery, and the integration with chemotherapy and immunotherapy. Accurate staging should include PET-CT and brain MRI. Thoracic RT should be initiated early during chemotherapy. Standard dose schedules include 45 Gy in 30 fractions (BID) or 66 Gy in 33 fractions once daily, using conformal techniques such as IMRT/VMAT, involved field nodal irradiation, respiratory motion management (e.g., 4D-CT, breath-hold) and image guidance (e.g., cone-beam CT [CBCT]). Concurrent chemotherapy with 4-6 cycles platinum-etoposide followed by consolidation durvalumab for up to two years is the standard of care in fit patients. Prophylactic cerebral irradiation (PCI) continues to represent the standard approach following treatment response; while hippocampal-sparing PCI and MRI surveillance strategies are being actively evaluated in ongoing studies. In selected cases, stereotactic body radiotherapy (SBRT) may be appropriate for medically inoperable early-stage disease without nodal involvement, and adjuvant RT can be considered for R1 resections or pN2 involvement. Emerging strategies, including adaptive RT, dose escalation and the integration of precision medicine have the potential to improve the therapeutic ratio. Integration with immunotherapy and/or novel agents, such as delta-like ligand 3 (DLL3)-targeted therapies, is under active investigation. Biomarker-guided treatment personalisation remains investigational. These updated European guidelines provide a comprehensive framework for standardized, high-quality care in stage I-III SCLC and establish a reference standard to harmonize radiotherapy approaches and inform the design of upcoming clinical trials.
This updated clinical practice guideline provides a practical, evidence-based approach for the management of adult soft tissue sarcoma of the extremity and trunk wall. The European Society for Radiotherapy and Oncology (ESTRO) formed a task force of 13 European experts, alongside 3 experts from the American Society for Radiation Oncology (ASTRO), to analyze current evidence, give recommendations and establish expert consensus in areas lacking strong evidence. Thirteen key questions were identified, encompassing indications for radiotherapy, pre- vs. postoperative radiotherapy, treatment preparation, patient positioning, target volume delineation, dose and fractionation, adverse events assessment, and dose guidance for organs of interest. Key recommendations were formulated and tabulated for each topic, addressing all identified key questions. Recommendations for 13 key questions were developed. Dosing for certain subtypes or clinical scenarios has evolved. Despite advancements in imaging, radiotherapy techniques, and personalized approaches, the core principles of treatment planning remain consistent with established practices. Innovative approaches, such as preoperative hypofractionation, radiotherapy combined with systemic therapies (immunotherapy, targeted therapies), and further histotype-specific dose tailoring, show promise; however, they should not be integrated into routine practice until further evidence is obtained. Preoperative conventionally fractionated radiotherapy, delivered using highly conformal techniques and volumetric imaging, followed by surgery, remains the preferred sequencing strategy for localized soft tissue sarcoma. Multidisciplinary evaluation at expert sarcoma centers remains essential for determining the optimal treatment approach for each patient.
We present the pre-planned co-secondary endpoint of two-year toxicity and early PSA response in the initial phase-I cohort of the SABR-Dual trial of two-fraction stereotactic radiotherapy (SABR) for localized prostate cancer. 20 patients with favorable intermediate- or low-risk prostate adenocarcinoma received a dose of 27 Gy in two fractions, with an optional integrated boost to 30 Gy. All underwent radiopaque hydrogel spacer and fiducial placement. MRI-based planning and real-time fiducial tracking were applied. Pre-planned secondary endpoints of two-year patient-reported quality of life based on EPIC-26, International Prostate Symptom Score (IPSS), and Sexual Health Inventory for Men (SHIM) questionnaires, toxicity based on CTCAEv5.0 assessment, and temporal PSA dynamics, were analyzed. A median increase in IPSS of 1 (IQR, -1.5-6) occurred at one-year, with a median decrease of 4 (IQR, 0.5-8.5) at two-years. Median SHIM score decreased at one- and two-years by 1 (IQR, -4.5-0.5) and 1 (IQR, -6.5-0.5), respectively. Rates of minimally clinically important change in EPIC-26 subdomains of urinary incontinence, irritative/obstructive, bowel, sexual, and hormonal symptoms decreased between one- and two-years, with the exception of sexual function, with rates of 5/19 (26.3%), 5/19 (26.3%), 6/19 (31.5%), 8/19 (42.1%), and 3/19 (15.8%), at one-year, and 2/19 (10.5%), 3/19 (15.8%), 1/19 (5.3%), 9/20 (47.4%), and 0/19 (0%), at two-years, respectively. Rates of grades 1/2 urinary toxicity at one- and two-years were 30%/30% and 5%/20%, while rates of grades 1/2 bowel toxicity were 0%/10% and 5%/5%, respectively. Mean and median PSA decreased from 5.66 and 5.35 ng/mL at baseline to 1.22 and 0.88 ng/mL and 0.42 and 0.31 ng/mL at 1- and 2-year follow-up, respectively, representing a decrease of 81.3% and 94.8%. Two-fraction prostate SABR using rectal spacing appears safe with acceptable intermediate-term toxicity and excellent PSA response.
This study aims to deeply mine the radiomic features of the primary tumor (GTVp) and cervical metastatic lymph nodes (GTVn) in nasopharyngeal carcinoma (NPC) to construct a multi-target synergistic prediction model. The goal is to achieve precise risk stratification for 5-year recurrence in patients at the initial diagnosis stage, providing a scientific basis for formulating individualized treatment and follow-up strategies. A total of 330 NPC patients were retrospectively included and divided into a training set (n = 150), an internal validation set (n = 65), and an independent external validation set (n = 115). Three target construction strategies-primary tumor alone (GTVp), fused target volume (GTVpn), and multi-target combination (GTVp&n, independent feature extraction followed by merging)-were employed. Core features were selected through dimensionality reduction using Least Absolute Shrinkage and Selection Operator (LASSO) regression combined with 10-fold cross-validation. Six machine learning algorithms, including XGBoost, GBDT, and MLP, were compared to determine the optimal scheme. Using SHAP interpretability analysis and multivariate logistic regression, a combined prognostic nomogram was constructed by integrating clinical factors and the radiomics score (R-score), and its generalizability was evaluated on the external validation set. For the single GTVp target, 21 radiomic features were selected via LASSO, among which the GBDT model performed best (training set AUC = 0.889). After streamlining to 6 features via SHAP analysis, the combined clinical nomogram yielded AUCs of 0.898, 0.879, and 0.857 in the training, internal validation, and external validation sets, respectively. Subgroup analysis of patients with lymph node metastasis showed that the XGBoost model using the GTVp&n strategy (independent feature extraction followed by merging) achieved the highest efficacy (training set AUC = 0.918), which was significantly superior to the single GTVp model (P = 0.035). The performance of the upgraded combined model was further enhanced, with the training set AUC reaching 0.934 and the external validation set AUC increasing to 0.879. Quantitative indicators (IDI = 0.139, NRI = 0.201) confirmed that incorporating lymph node heterogeneity features plays a key role in improving model accuracy and generalizability. This study developed and validated a synergistic radiomics model integrating information from both the primary tumor and metastatic lymph nodes. By simultaneously capturing the "source information" of the primary tumor and the "evolutionary information" of the lymph nodes, this synergistic model showed improved predictive performance compared to single-target models.. It offers potential quantitative evidence that may assist in formulating individualized intensive treatment strategies for NPC.
We have previously reported a single-arm, phase 1/2 trial against unresectable advanced or recurrent gastric cancer (GC) treated with a combination of radiotherapy and nivolumab (CIRCUIT trial). We present the 5-year updated results of the progression-free survival (PFS) and local control (LC) rates. We enrolled 41 patients with unresectable advanced or recurrent GC who developed progression after the primary and secondary chemotherapies with more than one tumor assessable by diagnostic imaging. Thirty-three patients had five or more tumors and 34 had two or more organs with cancer. The largest or symptomatic tumors were irradiated in 22.5 Gy/5 fractions/5 days. Three patients had multiple sites irradiated. Ten patients underwent irradiation of additional newly appeared tumors after the first irradiation. A total of 65 irradiated fields were evaluated. The median survival time and time to progression were 7.3 and 3.0 months, respectively. The overall survival and PFS rates were 29.6% and 7.5% at 1 year, 16.2% and 7.5% at 2 years, and 10.8% and 5.0% at 5 years, respectively. Two patients have lived without disease progression for >5 years. The median LC period was 49.8 months. The LC rates at 1, 2, and 5 years for the irradiated tumor were 84.8%, 71.8%, and 57.5%, respectively. Severe adverse events related to radiotherapy were not observed. The addition of radiotherapy to nivolumab therapy was safe and seemed to be beneficial for survival. Furthermore, a good LC rate was observed even with administering a palliative irradiation dose.
Toxicities after radiotherapy for head and neck cancer (HNC) often co-occur and share underlying mechanisms, yet most conventional and deep learning (DL) NTCP models predict only a single endpoint. By developing DL NTCP models which can predict multiple toxicities simultaneously, this study aimed to capture inter-toxicity relationships to improve prediction performance. A multi-institutional cohort of 1,418 HNC patients was used to develop and validate a multi-toxicity (MT) DL model, incorporating 3D dose distributions, CT scans, organ-at-risk segmentations and patient-related features, that simultaneously predicts five toxicities; aspiration, dysphagia, sticky saliva, taste alteration and xerostomia, all evaluated six months after treatment. Results are compared to conventional NTCP models, as well as a set of single-toxicity (ST) 3D DL models. The MT model outperformed both the conventional and ST models for dysphagia (AUC = 0.83 versus 0.81 and 0.82) and xerostomia (0.80 versus 0.75 and 0.78) prediction on the independent validation cohort. The latter models achieved better performance for sticky saliva (0.72 and 0.71 versus 0.69) and taste alteration (both 0.67 versus 0.71). The MT model achieved a higher AUC on aspiration than the ST model (0.71), but performed as well as the reference model (both 0.74). Within the external validation cohort, all models performed comparably to each other, with the MT model achieving a slightly higher average AUC (0.64) across all endpoints than the conventional and ST models (both 0.63). Sub-analyses revealed that the benefit of the proposed multi-toxicity modelling varied by endpoint. MT models offer comparable-and in some cases improved-performance over conventional single-endpoint approaches, indicating their promise for NTCP modelling. However, benefits are not uniform across all endpoints, highlighting the importance of considering toxicity-specific features when designing multi-toxicity models.
To revise and expand the 2011 Dutch guideline for radiotherapy in patients with cardiac implantable electronic devices (CIEDs), incorporating MR-linac treatment, proton therapy, and non-cardiac active implants. A literature review was performed using Embase and Ovid/Medline, covering studies from 2008 onwards. In addition, a survey was conducted among all Dutch radiation oncology centres to assess CIED-related incidents and current clinical practices. The updated guideline was developed by a multidisciplinary task group. The literature search identified 374 unique publications which were screened for relevance and analysed. Device malfunctions were found to occur predominantly with neutron-producing beam energies (> 10 MV photons or protons). The survey achieved a 100% response rate and reported only five resets, two cases of reduced battery longevity, and three transient devise malfunctions among 4942 radiotherapy patients with CIEDs treated in the Netherlands between 2011 and 2022. Based on these findings and literature, the updated guideline recommends that tachycardia therapies do not need to be deactivated during radiotherapy and that additional CIED checks are not required when photon energies ≤ 10 MV or electron beams are used and the cumulative CIED dose is < 10 Gy. Furthermore, recommendations for MR-linac treatment and non-cardiac implants are provided. The updated Dutch guideline introduces a risk-stratified approach based on neutron exposure rather than photon/electron dose alone. It simplifies monitoring protocols for nearly all radiotherapy patients treated with photons and electrons and extends guidance to newer treatment modalities and device types, thereby ensuring patient safety while streamlining radiotherapy workflows.
Reliable in vitro models to study radiotherapy response in triple negative breast cancer (TNBC) remain elusive. Traditional 2D cultures fail to reproduce the complex architecture and heterogeneity of solid tumors, which are essential factors influencing radiotherapy outcome. In contrast, 3D tumor spheroids better mimic key features of the tumor microenvironment, as cell-cell interactions and gradients of oxygen and nutrients. These features contribute to the formation of distinct zones within the spheroid - proliferative, quiescent, and necrotic, closely resembling the in vivo tumor structure and affecting radiotherapy efficacy. However, further investigation is needed to understand how radiotherapy affects cancer cells ultrastructure across the distinct layers of the tumor, as well as associated molecular pathways. Herein, we present a 3D TNBC spheroid platform that enables spatial characterization of tumor cell responses to clinically relevant radiotherapy across distinct spheroid regions. Radiotherapy decreased spheroids viability, while increasing cell size and the number of organelles, such as mitochondria, lipid droplets, rough endoplasmic reticulum and autophagic vesicles in surviving cells. Spheroids periphery, with higher oxygen availability and proliferation, exhibited the most pronounced organelle alterations after irradiation. Proteomic profiling revealed upregulated pathways linked to cell cycle progression and organelle fission, supporting G2/M cell cycle arrest. Enrichment of mitotic nuclear division, oxidative phosphorylation, ATP synthesis and lysosomal activity pathways suggest activation of repair and survival mechanisms following radiation-induced stress. Overall, this TNBC 3D model represents a promising platform for radiobiology research and for high-throughput screening of combinatory treatments to overcome radioresistance.
The FAST-Forward randomised nodal sub-study primary analysis showed non-inferiority for 5-year patient-reported arm/hand swelling following adjuvant breast/chest wall and axillary radiotherapy given in 26 Gy in 5 fractions (Fr) over 1 week compared to 40 Gy in 15Fr over 3 weeks. This subsequent analysis investigates the association between patient, tumour and treatment factors and development of long-term arm/hand swelling. Data from 469 patients randomised to adjuvant radiotherapy 40 Gy/15Fr, 27 Gy/5Fr or 26 Gy/5Fr to breast/chest wall and axilla (any or all levels 1-4) in the FAST-Forward nodal sub-study were included. DICOM-RT data were collected prospectively. ESTRO-defined axillary nodal levels 1-4, the axillary-lateral thoracic vessel juncture (ALTJ), and visible seroma were contoured retrospectively. Mean, maximum and minimum doses were extracted. Univariable and stepwise multivariable logistic regression were used to identify predictors of 5-year arm swelling. At 5 years, moderate/marked arm/hand swelling was reported by 39/299 (13%) patients and clinician-reported arm lymphoedema by 45/346 (13%). Multivariable analysis identified axillary lymph node dissection (ALND) (OR 3.70, 95% CI [1.61-8.48], p = 0.002) and BMI ≥ 35 kg/m2 (OR 3.31 [1.08-10.12], p = 0.036) as significant predictors of 5-year patient-reported moderate/marked arm/hand swelling. For 5-year clinician-reported arm lymphoedema, multivariable analysis identified ALND (OR 3.67 [1.55-8.69], p = 0.003) and number of positive lymph nodes (OR 1.08 [1.00-1.18], p = 0.049) as significant predictors. No significant associations were found between individual dosimetric parameters and 5-year arm swelling on multivariable analysis. Axillary surgery remains the main predictor of long-term arm lymphoedema following locoregional radiotherapy for node-positive breast cancer, supporting de-escalation of ALND to reduce this risk.
Severe oral mucositis (SOM) is a serious complication of radiotherapy for head and neck cancer (HNC) with limited prevention options. This study evaluated the efficacy of prophylactic recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) mouthwash in reducing SOM incidence and explored correlative immune biomarkers. In this randomized study, 100 HNC patients undergoing radiotherapy were assigned to a prevention group (n = 50), starting rhuGM-CSF mouthwash at radiotherapy initiation, or a treatment group (n = 50), initiating mouthwash only after onset of grade 1 OM. The primary endpoint was SOM incidence. Secondary endpoints included SOM duration, onset time, and quality of life (QoL). Exploratory immune biomarker analysis was performed. In the per-protocol analysis, the incidence of SOM in patients receiving prophylactic rhuGM-CSF treatment was significantly reduced (33.3% vs. 66.7%; HR = 0.31, 95% CI 0.17-0.57, p < 0.001), and the median duration was shorter (0 vs. 14 days, p < 0.001) compared to the treatment group. Below the 39.97% threshold, each unit increase in baseline percentage of activated CD4 + CD38+ / CD4 + T cells (%) was associated with a 9% reduction in the risk of SOM (HR = 0.91, 95% CI 0.87-0.95, p < 0.001). The prophylactic application of rhuGM-CSF mouthwash significantly decreases both the incidence and duration of SOM in patients with HNC receiving radiotherapy. An exploratory analysis suggested that the baseline percentage of activated CD4 + CD38+ / CD4 + T cells (%) could be a potential predictive biomarker for mucosal vulnerability and this hypothesis remains to be further verified.
The aim of GOAL27-6 was to evaluate quality of life (QoL) of patients and caregivers, following 27 Gy in 6 fractions palliative IMRT with early integration of palliative care (PC). This study included patients with head and neck squamous cell cancer unsuitable for curative treatment, who would accept upfront PC referral. The primary endpoints were QoL assessed with FACT-HN, and treatment-toxicity with CTCAE_v5.0. The secondary endpoints included caregivers' QoL measured with CarGoQoL, treatment-response and survival. Improvement and deterioration in QoL for FACT-HN was pre-defined as ≥ 5% & ≥-10% of the total score respectively, and ≥ 3.65 & ≥-4.13 global-index points respectively for CarGoQoL. The mean FACT-HN scores of 32 eligible patients increased by 5% and 8% at week-12 and 18 (standard deviation SD = 26) post-27 Gy/6f respectively. Seventeen patients (53%) experienced QoL-improvement, 6 (19%) maintained the same, 9 (28%) reported deterioration. There was no ≥ Grade 3 treatment-toxicity. Of the 30 eligible caregivers: 20 (67%) experienced QoL-improvement, 8 (27%) remained the same, 2 (7%) deteriorated. The mean CarGoQoL global-index increased by 6.65(SD = 22) and 8.40(SD = 16) points at week-12 and 18 respectively. Eighteen patients (56%) had complete/partial response, 7 (22%) stable disease and 7 (22%) progressed. The median survival of patients with improved/maintained QoL was 10 months, compared to 4.4 months in patients with deteriorated QoL (p < 0.001). The Spearman correlation between treatment-response and patients' QoL was ρ = 0.23 (p = 0.13). Combined 27 Gy/6f IMRT with early PC integration can overall improve patients and caregivers' QoL. With weak correlation between treatment-response and QoL, patients/caregivers' QoL goals may benefit from early exploration.
Triple-negative breast cancer (TNBC) still poses an important clinical challenge due to its aggressiveness, notwithstanding the increasing amount of treatment options. While radiation therapy (RT) is important for TNBC management, dose-limiting side effects limit its efficacy. FLASH-RT, delivered with ultra-high dose rates, has shown anti-tumour effects comparable to conventional dose rate RT (CONV-RT) but with reduced normal tissue side effects, offering the potential of dose escalation to treat aggressive tumour subtypes such as TNBC. In this study, we investigated TNBC responses to FLASH-RT across gene transcription, immune infiltration, and anti-tumour efficacy. Using subcutaneous and orthotopic 4 T1 and MDA-MB-231 murine TNBC models, female BALB/c or Swiss nude mice received single (14 or 20 Gy) or fractionated (5 × 5.2 or 10 × 3 Gy) doses of either CONV-RT (0.2 Gy/s) or FLASH-RT (5-5.79 × 10⁶ Gy/s). Tumour growth was monitored, and 4 T1 tumours were collected at 24 h, 5 days, and 2 weeks post-irradiation for histology, flow cytometry, and bulk RNA sequencing. All regimens demonstrated iso-efficacy between FLASH and CONV-RT in delaying tumour growth. RNA sequencing revealed that, 24 h post-irradiation, FLASH-RT significantly preserved expression of chemokines (NES = 2.516), including CXCL9, 10 and 11 which are critical for T cell function. Additionally, FLASH-RT retained interferon alpha and gamma signalling (NES = 2.998; 3.235) via the ISGF3 complex, resulting in interferon-stimulated genes expression. While CONV-RT downregulated these genes, histology and flow cytometry showed no differences in immune cell infiltration between modalities. We hypothesize that FLASH-RT's conserved expression of negative regulators of interferon type I and II (NES = 2.108 and 1.784 respectively), but also negative regulators of inflammation (NES = 1.88), including PD-L1 and IL18BP, may underlie this discrepancy. In summary, while FLASH-RT and CONV-RT are equally effective in delaying tumour growth and modulating the immune response in murine TNBC, transcriptomic analysis uncovered distinct immunomodulatory profiles, suggesting nuanced mechanisms that warrant further investigation.
With the long-term survival of paediatric rhabdomyosarcoma patients improving, the impact of late adverse effects becomes more important. These late effects in head-neck-rhabdomyosarcoma survivors include poor cosmesis associated with facial deformation. This study aims to correlate facial deformation with radiation dose and propose new dose-effect models. We evaluated 3D facial images of children treated with radiotherapy enrolled in our multi-center cross-sectional study with a primary head-neck-rhabdomyosarcoma. Facial deformation was calculated from 3D image analysis at follow-up and compared to a healthy control population (n = 537). The radiation dose delivered to all individual facial bones and sutures was extracted from original radiotherapy plans. Dose-effect probability curves were constructed by converting the dose to its equivalent 2 Gy/fraction EQD2 using binary logistic regression. Thirty-four survivors with a median follow-up of 9.2 years were included. Survivors with facial deformation all received significantly higher mean doses to the corresponding bony structures (p < 0.001). The ethmo-maxillary complex shows increased susceptibility for facial deformation at 28GyEQD2 and a 50% probability of growth deformation at 51GyEQD2. The mandibular complex shows increased growth deformation probability at 26GyEQD2 and a 50% probability at 41GyEQD2. The threshold for increased risk of bone deformation for individual facial bones varied from 26 GyEQD2 to 43 Gy EQD2 and a 50% probability for deformation varied from 44 Gy EQD2 to 55 Gy EQD2. Dose thresholds for specific facial bones impacting cosmesis in survivors of paediatric sarcoma are shown. These data are essential to improve treatment planning thereby limiting the debilitating late adverse effect of facial deformation.
This single-arm phase II study evaluated the safety and efficacy of moderately hypofractionated radiotherapy (RT) after radical prostatectomy (RP) for prostate cancer in the adjuvant or salvage setting. Eligible patients were men aged ≥ 20 years who had undergone RP and were scheduled for adjuvant or salvage RT, with an Eastern Cooperative Oncology Group performance status of 0-2 and no prior pelvic RT or distant metastasis. RT consisted of 54 Gy in 18 fractions delivered with volumetric modulated arc therapy to the prostate bed, with optional pelvic lymph nodal bed irradiation. The primary endpoint was the incidence of grade ≥ 2 acute genitourinary (GU) and gastrointestinal (GI) toxicity. Secondary endpoints included biochemical recurrence-free survival (bRFS), toxicity, and quality of life (QoL). Between December 2018 and November 2021, 55 patients received protocol treatment. The median follow-up was 37.3 months. Salvage RT was performed in 49 patients (89%) and adjuvant RT in six (11%); 53% received concurrent androgen deprivation therapy. Grade ≥ 2 acute GU and GI toxicities occurred in 5.5% and 34.5% of patients, respectively; GI events were predominantly grade 2, with one patient (1.8%) experiencing grade 3 small bowel obstruction. During the relatively short follow-up period (median, 37.3 months), grade ≥ 2 late GU and GI toxicities were observed in 14.6% and 21.8% of patients, respectively. The 3-year bRFS was 65.8% (95% confidence interval, 51.1-77.1). QoL was largely maintained, with transient bowel symptoms resolving within three months. Moderately hypofractionated RT of 54 Gy in 18 fractions after RP achieved favorable biochemical control with generally manageable toxicity, supporting its feasibility.
Prostate Cancer Study 5 (PCS-5) is a phase III, randomized controlled trial comparing conventionally fractionated radiotherapy (CFRT) vs. hypofractionated radiotherapy (HFRT) exclusively in patients with high-risk prostate cancer (PCa). This post hoc analysis evaluates differences in efficacy outcomes as well as genitourinary (GU) and gastrointestinal (GI) toxicities between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). PCS-5 randomized patients in a 1:1 ratio to CFRT (76 Gy in 38 fractions) or HFRT (68 Gy in 25 fractions). All patients received long-term androgen suppression (median duration: 24 months) and pelvic radiation therapy (RT). Acute toxicities were defined as ≤ 180 days post-RT, and delayed toxicities > 180 days using CTCAE v4. Multivariable logistic regression analyses were performed for acute and delayed toxicities, adjusting for clinical factors. Efficacy analyses utilized Cox proportional hazards regression models. Among 329 patients, 296 were included in this study. IMRT reduced acute G2 + GI toxicities (OR 0.50; 95% CI, 0.29-0.91; p = 0.023), delayed G2 + GI toxicities (OR 0.36; 95% CI, 0.16-0.82; p = 0.015), and increased acute G1 + GU toxicities (OR 1.77; 95% CI, 1.07-2.95; p = 0.03) compared to 3D-CRT. Biochemical failure-free survival, distant metastasis-free survival, and overall survival did not significantly differ between techniques. In PCS-5, HFRT is a standard treatment for high-risk PCa receiving external beam RT. In this post hoc analysis, IMRT was associated with lower acute and delayed G2 + GI toxicity than 3D-CRT, with a modest increase in acute G1 + GU toxicity and no differences in efficacy. Within the limitations of this non-randomized comparison, IMRT appears to be the preferred technique.
To determine the dynamic complexity of symptom networks in patients with head and neck cancer during radiotherapy to inform precise symptom management. Symptom severity was assessed using the Chinese version of the MD Anderson Symptom Inventory-Head & Neck module at four time points(T1, 1 week before radiotherapy; T2, 2-5 sessions; T3, 16-20 sessions; T4, 30-33 sessions). Longitudinal predictive relationships among the 20 symptoms were analyzed using a cross-lagged panel network (CLPN), and the accuracy and stability of the network were evaluated using nonparametric bootstrap methods. As a directed network derived from longitudinal data, the directionality within the CLPN was also examined using out-expected influence (out-EI) and in-expected influence (in-EI). Among 366 patients analyzed, symptom incidence and severity increased significantly during radiotherapy, peaking at T3. Dry mouth, taste disturbance, and loss of appetite were the most prevalent and severe symptoms. Oropharyngeal pain exhibited an oscillatory driver pattern: negative (out-EI = -2.48) → positive (out-EI = 2.30) → negative (out-EI = -2.21). Loss of appetite displayed a recurrent driver (out-EI = 1.65)-latent (out-EI = 0.35)-redriver (out-EI = 1.20) trajectory. Drowsiness transitioned from a mid-radiotherapy driver (out-EI = 1.43) to a late-phase receiver (in-EI = 1.61). The symptom network demonstrated good stability from T2 to T4. This study presents the first longitudinal network analysis of symptom dynamics during radiotherapy for HNC. The findings lay the groundwork for stage-specific interventions to optimize symptom management and improve patient quality of life.
To evaluate the image quality of dual-energy CT (DECT) virtual monoenergetic imaging (VMI) in rectal cancer and to investigate its value for gross tumor volume (GTV) delineation in radiotherapy. Twenty-nine patients with rectal cancer receiving neoadjuvant chemoradiotherapy were prospectively enrolled. Each patient underwent contrast-enhanced DECT and 3.0 T MRI on the same day. Lesion contrast (LC), contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were assessed for VMI from 40-200 keV and synthetic 120 kVp CT (S120kVp), with the optimal monoenergetic image (VMIEopt) determined accordingly. Three radiation oncologists independently assessed VMIEopt, S120kVp, and T2WI-MRI for overall image quality and tumor delineation, and delineated GTVs. T2WI-MRI served as the reference. Dice similarity coefficient (DSC) was used to compare delineation performance, with further analysis of interobserver agreement and cranial-caudal margin identification. Venous-phase 40 keV VMI (VMIEopt) showed significantly higher LC, CNR, and SNR than S120kVp (p < 0.0001). Subjective scores of VMIEopt were comparable with MRI for both overall image quality (p = 0.040) and tumor delineation (p = 0.449). The concordance between VMIEopt- and MRI-defined GTVs was significantly higher than that between S120kVp- and MRI-defined GTVs (mean DSC: 0.83 ± 0.04 vs 0.67 ± 0.10, p < 0.0001). In patients with high registration accuracy, the DSC for the VMIEopt-MRI comparison further improved to 0.86 ± 0.01. Interobserver agreement was superior for VMIEopt compared with S120kVp (0.82 ± 0.05 vs 0.76 ± 0.07, p < 0.001). Cranial and caudal margin errors were also significantly reduced when using VMIEopt compared to S120kVp. Venous-phase 40 keV DECT VMI demonstrated objectively and subjectively superior image quality compared with S120kVp, significantly improving GTV delineation accuracy, interobserver consistency, and cranial-caudal margin identification. It may serve as a reliable imaging tool to balance tumor control and normal tissue sparing in rectal cancer radiotherapy.
Muscle loss during adjuvant radiotherapy is associated with poor survival outcomes in patients with oral cavity cancer (OCC). This study aimed to develop and validate an explainable machine learning model to predict muscle loss. This study included 1,024 patients with OCC (derivation cohort, 636 patients; external validation cohort, 388 patients) who underwent surgery and adjuvant radiotherapy between 2010 and 2021. Muscle mass was measured using computed tomography at the C3 vertebral level before and after radiotherapy, with "muscle loss" defined as a decrease of ≥4.2%. Random Forest (RF), eXtreme Gradient Boosting (XGBoost), and Categorical Boosting (CatBoost) models were trained using clinical and dosimetric data to predict muscle loss. Model performance was evaluated using the area under the curve (AUC). The SHapley Additive exPlanations method was applied for interpretation. Muscle loss occurred in 166 (26.1%) and 98 (25.3%) patients in the derivation and external validation cohorts, respectively. The RF model outperformed XGBoost and CatBoost in the external validation cohort (AUC: 0.913, 0.892, and 0.904, respectively). Top predictors included pre-radiotherapy Mini-Nutritional Assessment scores, mean radiation doses to the superior/middle pharyngeal constrictor muscle and supraglottic larynx, and chemotherapy. A nonlinear dose-toxicity relationship was observed between the mean dose to the swallowing structures and muscle loss. The model provided patient-level interpretations, identifying specific contributors for individual cases. An explainable model could predict muscle loss and identify specific risk factors. This approach may enable clinicians to tailor interventions and radiotherapy planning to mitigate muscle loss.
Vaginal and sexual symptoms after radiotherapy for anal cancer are recognised but not well characterised longitudinally. To describe the prevalence, severity, and trajectories of vaginal and sexual symptoms up to five years after curative-intent radiotherapy for anal cancer, using clinician-graded toxicity and validated patient-reported outcomes. We conducted a sub-study within the DACG-I prospective cohort (NCT05570279), which included women with anal cancer treated with curatively-intended radiotherapy between 2015-2021. Patient-reported outcomes (EORTC QLQ-CR29, QLQ-CX24) and clinician-graded vaginal toxicity (CTCAE v4.0) were collected at baseline and 1, 3, and 5 years. Symptom prevalence was summarised descriptively. Longitudinal changes were evaluated using linear mixed-effects models on linearly transformed EORTC scores. Of 231 enrolled women, 221 provided baseline data. Sexual activity was reported by approximately 25% of participants at each time point. CTCAE grade 2-3 events were uncommon but increased for selected symptoms, including vaginal dryness. Patient-reported symptoms were more frequent. Among sexually active women, moderate to severe vaginal dryness, shortness and tightness affected 28-42% from one year onwards. EORTC scores showed clinically important deteriorations from baseline to one year in dyspareunia, vaginal and sexual symptoms, sexual worry, and sexual enjoyment, with limited recovery over time. Subgroup differences by age, T stage and prescribed dose were small and inconsistent. Vaginal and sexual symptoms after radiotherapy for anal cancer are common, develop early and show little recovery over five years. Systematic assessment and structured survivorship pathways are needed to address these long-term effects.
Oral mucositis (OM) is a common and painful complication in patients with head and neck cancer (HNC) undergoing radiotherapy or chemoradiotherapy. Photobiomodulation therapy (PBMT) historically referred to as low-level laser therapy (LLLT) has been suggested as a treatment for reducing OM severity and pain. In this prospective, double-blind clinical trial, 163 patients were screened, and 53 patients with two comparable OM lesions were ultimately included in the analysis. One lesion received PBMT (660 nm, 150 mW, 5 J per point, twice weekly), and the other received sham treatment as control. Lesion severity and pain were assessed weekly using the Oral Mucositis Assessment Scale (OMAS) and the Visual Analog Scale (VAS) until complete healing or two weeks after radiotherapy. PBMT significantly reduced OMAS and VAS scores compared to control lesions. VAS reduction was observed from the first week, whereas OMAS decreased from week three. Complete healing occurred in 52.4% of intervention lesions versus 11.9% of control lesions (P < 0.001). PBMT accelerated recovery without adverse effects. According to multivariable regression analysis, Primary cancer site was the independent predictive factor of healing of radiation-induced oral mucositis following PBMT (aOR 5.78, 95% CI 1.28-36.0, P = 0.03). PBMT was associated with a significant reduction in pain and lesion severity in patients with radiation-induced oral mucositis undergoing head and neck radiotherapy. These findings support its potential therapeutic role as a supportive care intervention.