Acta Oncologica最新文献

Background and purpose: This multicentre, retrospective study aimed to develop a predictive model for radiation-induced dysphagia in head and neck cancer patients, focusing on the role of gross tumour volume (GTV) to high dose CTV (CTV1) margin size and dose-related factors. Unlike previous studies focused on peak or single time-point dysphagia, this study modelled symptom trajectories using repeated follow-up data for a more complete picture. Patient/material and methods: Between 2010 and 2015, 1,948 patients with pharyngeal or laryngeal squamous cell carcinoma received definitive intensity-modulated radiotherapy (IMRT) at three Danish centres. Data included physician-rated dysphagia (grade 0-4), tumour and treatment characteristics, and AI-based segmentations of organs at risk (OARs). Predictors included GTV-CTV1 margin size, mean doses to the oral cavity and pharyngeal constrictor muscles (PCM), GTV volume, chemotherapy, tumour site, fractionation, nimorazole, sex, smoking status, baseline dysphagia, and age. A logistic ordinal mixed-effects model was fitted with patient ID as random effect. Data were split into training (70%) and test (30%) sets. Model performance was assessed using calibration plots and area under the curve (AUC).

Results: After excluding incomplete cases, 1,685 patients (7,829 visits) were analysed. GTV-CTV1 margin size was not significantly associated with dysphagia, although larger margins correlated with higher OAR doses. Higher doses to the lower PCM (odds ratio [OR] = 1.30 per 5 Gy) and oral cavity (OR = 1.32 per 5 Gy) increased risk. The model demonstrated good calibration and robust discrimination (AUC = 0.77-0.84).

Interpretation: Radiation dose to the oral cavity and lower PCM were the strongest modifiable predictors of dysphagia risk. Margin size was not independently associated, possibly due to confounding by clinical judgement.

Background and purpose: Chromosomal rearrangements involving KMT2A (KMT2A-r) occur in 20% of paediatric acute myeloid leukaemia (AML). Previous studies reported that the outcome depends on the specific fusion partner. The study aimed to report the outcomes of paediatric KMT2A-r AML patients and to assess the impact of different fusion partners. Patient/material and methods: We retrospectively analysed 610 paediatric patients with intermediate-risk (IR) AML diagnosed at Children's Cancer Hospital Egypt, from January 2008 to December 2021. Patients were assigned to four groups based on fusion partner.

Results: Of 610 patients diagnosed with IR-AML, 150 (24.6%) had KMT2A rearrangements. KMT2A-r was significantly associated with hyperleukocytosis (P = 0.029), central nervous system (CNS) disease (P = 0.003), monocytic differentiation (P = 0.001), additional cytogenetic abnormalities (ACA) (P = 0.04), and complex karyotype (P = 0.001). Fusion partner, t(9;11) (p22;q23) (9p22/KMT2A::MLLT3 fusion) was most prevalent (40.8%). KMT2A-r was an independent predictor of relapse with a cumulative incidence of relapse (CIR) of 46% versus 30% in KMT2A negative group (P = 0.006). Within the KMT2A-r group, ACA and complex karyotype adversely affected the outcome with 5-year overall survival (OS) of 34% versus 53% (P = 0.027) and 26% versus 51% (P = 0.004), respectively. Outcome varied depending on fusion partner. Event-free survival (EFS) ranged from 50% to 17%, OS from 54% to 27%, and CIR from 75% to 38%.

Interpretation: KMT2A-r is an independent prognostic factor for relapse, and presence of ACA and a complex karyotype in KMT2A-r patients is associated with poorer outcomes, emphasising the need for aggressive and innovative therapeutic strategies.

Background and purpose: Children treated with radiotherapy (RT) for a brain tumour often exhibit neurocognitive impairment and report lower quality of life (QoL) later in life. The aim of this nationwide cross-sectional cohort study was to explore the impact of RT dose to brain organs at risk (OARs) on neurocognition and QoL in long-term survivors of childhood brain tumours. Patient/material and methods: A total of 132 survivors of childhood brain tumours, diagnosed from 2001 to 2017 in Denmark, underwent neurocognitive tests and QoL questionnaires at least 5-years post-diagnosis. Neurocognitive assessments were complete and available for 86 patients (61 no-RT/25 RT), and QoL scores for 107 (79 no-RT/28 RT). Mann Whitney U-tests were used to compare scores between no-RT and RT groups. For scores impacted by RT, OAR-specific robust linear regressions were performed to evaluate RT dose effects while adjusting for potential confounders.

Results: Clinically significant overall cognitive impairment was observed for 55% of the neurocognitive sub-cohort, with younger age at treatment time as a significant risk factor, while hydrocephalus status had no impact. There were no statistically significant differences on neurocognitive tests between the RT and no-RT group. However, patients treated with RT had significantly lower scores on the physical and social functioning QoL domains, with mean dose to the pituitary gland and left hippocampus, respectively, as significant predictors.

Interpretation: This cross-sectional study indicates that RT dose-effects, particularly in the pituitary gland and left hippocampus, might contribute to reduced QoL in survivors of childhood brain tumours.

Background and purpose: One of the factors influencing disease control and toxicity risk after radiotherapy is selection of treatment volume margin. This study evaluates whether different gross tumour volume (GTV) to high-dose clinical target volume (CTV1) margins impact dysphagia in a cohort of head and neck squamous cell carcinoma (SCC) patients. Patient/material and methods: Data of patients receiving primary IMRT-based radiotherapy for SCC for the oropharynx, hypopharynx, and larynx at three treatment centres between 2010 and 2015 were retrospectively collected. Treatment planning followed two DAHANCA guideline periods: pre-2013 (varying GTV-CTV1 margins), and post-2013 (isotropic 5 mm margin). Treatment plans were collected for 1,913 patients. GTV-CTV1 margins were calculated as median surface distance from GTV to CTV1. Dysphagia was graded using modified DAHANCA ordinal scale. For each patient, the highest score of dysphagia during 5-year follow-up period was chosen for analysis.

Results: Dysphagia data were available for 1,706 patients (89%). The median GTV-CTV1 margin was 9.0 mm in 2010-2012 and 4.7 mm in 2013-2015. The severity of dysphagia was more pronounced in patients treated during 2010-2012 (p = 0.003). Predictors of grade ≥ 2 dysphagia included larger GTV (odds ratio [OR]: 1.7; p < 0.001), larger GTV-CTV1 margin (odds ratio [OR] of 1.3 per cm; p = 0.04), and tumour localisation other than oropharyngeal p16+carcinomas (p = 0.002). Male sex, non/previous smoking status, and application of chemotherapy were associated with less severe dysphagia.

Interpretation: Tumour volume and GTV-CTV1 margin are dominant geometric parameters influencing dysphagia risk following curative radiotherapy.

Background and purpose: Lung cancer patients have an increased risk of adverse employment outcomes. However, limited research exists on the association between socioeconomic position (SEP) and employment status in this cancer group. This study explored the influence of SEP on employment status after a lung cancer diagnosis. Patient/material and methods: This population-based cohort study included all working-age Danish residents diagnosed with lung cancer between 2000 and 2015. Logistic regression analyses were conducted to assess the association between socioeconomic variables (education, income, sick leave, and work status before diagnosis), and working and disability pension 3 years after diagnosis.

Results: A total of 1,946 lung cancer patients were included. High income and long education were associated with higher odds of working, odds ratio (OR) = 2.31 (1.65-3.24) and OR = 1.92 (1.15-3.21), respectively, and lower odds of disability pension, OR = 0.19 (0.11-0.33) and OR = 0.30 (0.13-0.70), respectively. Moreover, sick leave and being out of work before diagnosis were associated with lower odds of working, OR = 0.25 (0.13-0.46) and OR = 0.32 (0.24-0.43), respectively, and higher odds of disability pension, OR = 3.73 (2.14-6.50) and OR = 2.88 (2.14-3.87), respectively.

Interpretation: Lung cancer patients with low SEP are less likely to be employed and more likely to receive disability benefits. Therefore, rehabilitation to support socioeconomically disadvantaged lung cancer patients is needed.

Background and purpose: Treatment-related diarrhea is a challenge for patients treated with chemo-radiotherapy (CRT) for anal cancer in a curative setting. This study aims to investigate dosimetric and clinical predictors of acute and late diarrhea for patients treated with CRT or radiotherapy (RT) alone for anal cancer. Additionally, to investigate different bowel contouring methods ability to predict diarrhea. Patient/material and methods: Patients treated with CRT or RT alone in the prospective, observational DACG-I Plan-A study (2015-2021) were included. Toxicity endpoints were acute grade ≥2 diarrhea, and late grade ≥1 diarrhea recorded at 1 year after treatment (Common Terminology Criteria of Adverse Events (CTCAE), v4.0). Bowel volumes were contoured on the planning computed tomography (CT) as bowel cavity, bowel bag, individual bowel loops, and terminal ileum. Dosimetric variables included V15Gy, V30Gy, and V45Gy for the different bowel volumes. Clinical variables included tumor size, N-stage, and chemotherapy regimen. Logistic regression was used to evaluate the association between variables and toxicity.

Results: Of the 290 patients included in this study, 116 (40%) experienced acute grade ≥2 diarrhea, and 56 of 256 (22%) had late grade ≥1 diarrhea. Patients treated with 5-FU/Capecitabine had a threefold higher risk of acute diarrhea compared to those receiving weekly Cisplatin or RT alone (p < 0.001). A trend indicating an increased risk of acute grade ≥2 diarrhea for patients with larger bowel volumes receiving radiation was observed. This was most pronounced for bowel bag V30Gy (p = 0.09); however, results from the different bowel contouring methods were similar. No parameters were predictive of late diarrhea.

Interpretation: No dosimetric or clinical predictors of late diarrhea were found and only a trend was found between higher dose to bowel and risk of acute diarrhea. Treatment with 5-FU/Capecitabine showed a notable association with acute diarrhea. No contouring method was superior in predicting diarrhea.

Background and purpose: Radiotherapy for head and neck cancer must balance tumour control with late toxicities such as dysphagia and xerostomia. Recent retrospective studies suggest that the margin from the gross tumour volume (GTV) to the high-dose clinical target volume (CTV1) may not be critical for local control, while larger irradiated volumes increase the risk of toxicity. The study quantifies potential reductions in dose to organs at risk (OARs) and predicted dysphagia risk when the standard 5 mm GTV-to-CTV1 margin is eliminated in oropharyngeal cancer. Patient/material and methods: Retrospectively 30 oropharyngeal cancer patients treated consecutively during 2023 according to the DAHANCA guidelines (5 mm GTV-to-CTV1 margin) were selected. For each patient, a standard plan and a modified experimental plan (CTV1 = GTV, and CTV2 reduced by 5 mm accordingly) were generated using Pinnacle3 Auto-Planning. All plans met the DAHANCA target coverage and OAR dose constraints. Dose-volume data for relevant OARs were extracted and compared in MATLAB. Normal tissue complication probability (NTCP) model for dysphagia was applied.

Results: Margin elimination reduced high-dose CTV volumes by 70%, yielding significant dose reductions to multiple OARs. Mean doses to the upper/middle pharyngeal constrictors decreased by around 4-5 Gy (p < 0.001) and to the contralateral submandibular gland by ~5 Gy (p < 0.001). These dosimetric gains correspond to an estimated median ΔNTCP of 6.0% of late grade ≥ 2 dysphagia. Target coverage and conformity were maintained in all plans.

Interpretation: Omitting the high-risk CTV margin can substantially reduce the dose to dysphagia--associated OAR without compromising target coverage. This approach shows promise for improving patient-reported swallowing outcomes and warrants clinical evaluation.

Background and purpose: Magnetic resonance imaging-guided radiotherapy (MRIgRT) enables precise tumour targeting through adaptive planning, which is particularly relevant for glioblastoma due to its dynamic morphology. Gadolinium-based contrast agents (GBCAs) enhance tumour visibility, but frequent use during MRIgRT raises safety concerns related to cumulative gadolinium exposure. This study investigated the feasibility of a reduced GBCA dose protocol for patients with glioblastoma undergoing MRIgRT, aiming to balance tumour conspicuity with minimisation of GBCA-related risks. Patient/material and methods: Nine patients with glioblastoma received hypo-fractionated MRI-Linac radiotherapy (10 × 3.4 Gy) with MRI performed with either full-dose, half-dose or no GBCA enhancement. Online gross tumour volume (GTV) delineation was performed by radiation oncologists, while offline GTV delineation was independently conducted by an expert neuroradiologist on GBCA-enhanced scans. Objective assessment using automatic thresholding and a structured Likert-scale evaluation were also performed.

Results: During online adaptation, GTV volumes generally remained stable or increased, whereas offline expert assessments revealed a general volume reduction and systematic volume underestimation with half-dose scans (~18%). Relative delineation volume discrepancies were most pronounced in small tumours. Structured radiologist feedback reported lower confidence, tumour conspicuity and image quality in half-dose scans, particularly for small lesions. Otsu's thresholding revealed reduced edge definition with decreasing contrast dose. No signs of GBCA retention were observed between fractions.

Interpretation: Reduced-dose GBCA-protocols are feasible. Full-dose contrast is recommended at key fractions (e.g. baseline and mid-treatment) and for small tumours, with half-dose imaging reserved for selected intervals or larger tumours. This hybrid approach may balance safety and imaging precision in adaptive MRIgRT.