Acta Oncologica最新文献

Background and purpose: Sexual dysfunction is a common consequence of pelvic radiotherapy, influenced by psychological, physical, social, and relational factors. Research has focused on vaginal dose and stenosis in females and penile bulb dose and erectile dysfunction in males, with limited attention to domains, such as arousal, desire, and satisfaction. In the Danish Colorectal Cancer Radiotherapy Group, we aimed to: (1) Develop an atlas of sexual function-related organs at risk and (2) Evaluate if these organs at risk could be spared without compromising target coverage in rectal cancer radiotherapy planning. Patient/material and methods: A multidisciplinary approach was adopted, involving oncology, physics, psychology, surgery, and radiology. MRI-based anatomical definitions were established, and an atlas was created for both males and females, including inferior hypogastric plexus, pudendal vessels/Alcock's canal, neurovascular bundle, penile bulb, vagina, paracolpium, and bulboclitoris. For comparative planning standard and sexual function-sparing plans were created for each patient.

Results: A national consensus atlas for sexual function-related organs at risk was developed. Standard plans (n = 15) and sexual function-sparing plans (n = 15) for seven males and eight females were compared. Sparing of pudendal vessels and bulboclitoris was feasible without compromising the standard plan. For sexual function-related organs at risk in or close to the target, D2% could often be improved.

Interpretation: Our consensus-based delineation and planning demonstrate that radiation dose to many sexual function-related organs at risk can be spared or optimized without compromising target coverage or dose to standard organs at risk. Future work includes implementing patient-reported outcomes and integrating these new organs at risk into standard radiotherapy planning.

Background and purpose: We present a systematic review of breast dose metrics reported in lymphoma patients receiving radiotherapy and provide reporting recommendations for breast dose in future publications.

Methods and materials: Studies reporting breast doses in lymphoma radiotherapy published between January 2000 and May 2023 were included. Frequency of reporting factors likely to affect breast dose were calculated. Doses for the most frequently reported metrics (mean breast dose (MBD) (Gy, percentage of prescription), V5Gy and V10Gy (%)) were calculated across articles and compared for target volume approaches, radiotherapy techniques, and inclusion of the axilla.

Results: Thirty-four distinct breast dose metrics were found across 57 articles. MBD was the most commonly reported. Axilla irradiation significantly increased MBD, V5Gy and V10Gy, yet 21 articles reported breast doses for a mixed cohort with respect to axillary irradiation. Forty-eight of 57 articles did not report the breast contouring guidelines used. Among articles reporting MBD for proton or butterfly-volumetric modulated arc therapy (VMAT), there was no significant reduction in breast radiation dose for protons compared to butterfly-VMAT.

Interpretation: A wide variety of breast dose metrics are reported in the literature, making it challenging to pool breast tissue exposure data in lymphoma radiotherapy. Factors shown in individual studies to affect breast dose should be reported more systematically to enable large scale analysis. Reporting the presence/absence of axillary irradiation is crucial, due to the significant effect on breast dose. We provide reporting recommendations for breast dose metrics to improve research into radiotherapy-induced breast cancer.

Background and purpose: This study investigated prognostic biomarkers in oropharyngeal squamous cell carcinoma (OPSCC), with a focus on tumors related to human papillomavirus (HPV) infection and potential molecular effects of tobacco smoking, as smokers with HPV+ OPSCC often have poorer outcomes.

Patients/material and methods: We first analyzed 56 previously untreated OPSCC patients (exploration cohort), assessing HPV status, gene expression related to hypoxia, tumor subtype, and radiosensitivity, together with next-generation sequencing (NGS) of cancer-related genes. A custom NGS panel was subsequently designed and validated in 162 patients from the DAHANCA 19 randomized controlled trial (RCT), all treated with curative (chemo-)radiotherapy.

Results: In the exploration cohort (40 HPV+, 79%), the most common molecular events in HPV+ tumors were PIK3CA and ATR mutations and chromosome 3q amplification. ATR and CREBBP mutations occurred more often in heavy smokers (>10 pack-years), but these associations were not confirmed in the DAHANCA 19 cohort. No specific smoking-related mutational signature or link to TP53 mutations was observed. In the DAHANCA 19 cohort, 17 locoregional failures (LRF) occurred among 128 HPV+ patients. No unifying molecular features were identified. However, mutations in NFE2L2 and CASP8, as well as amplifications of 3q genes (BCL6, SOX2), were associated with LRF.

Interpretation: In HPV+ OPSCC, only few molecular alterations appear to act as drivers or prognostic biomarkers. Importantly, no molecular features of tobacco smoking exposure were identified, and the mechanism behind the worse prognosis in smokers remains unclear.

Background and purpose: The aim of this controlled cross-sectional, and population-based study was to evaluate adverse health outcomes (AHOs) 3 years after curative radiotherapy (RT) + androgen deprivation therapy (ADT). We also assessed Global Health/Quality of Life (QoL).

Patients/material and methods: The Cancer Registry of Norway (CRN) provided data on prostate cancer (PCa) patients diagnosed in 2017-2019. All had been treated with RT+ ADT. All had completed EPIC-26 and EORTC QLQ-C30 about 3 years after RT start (n = 663). ADT duration was stratified: Short (< 9 months), intermediate (9-18 months) and long ADT (18-24 months). A group of controls were established from the general population (n = 1,817). Outcome measures were the urinary irritative/obstructive domain summary score (DSS), the bowel and sexual DSSs (EPIC-26) and QoL (EORTC QLQ-C30).

Results: Compared to controls, patients had clinically important lower bowel, and sexual mean scores. Urinary irritative/obstructive DSS levels were similar. Overall, 43% (PCa patients) and 20% (controls) reported major sexual problems. In patients aged < 75 years, longer than short ADT duration significantly decreased sexual DSS. QoL was relatively unaffected. Low response rates, selection bias and a lack of pre-treatment data represent the studys´ limitations.

Conclusion and interpretation: Three years post-RT+ADT, PCa patients describe clinically important lower EPIC-26 bowel and sexual DSS compared to controls. Sexual domain levels decreased with increasing ADT duration, particularly in patients < 75 years. Our observations indicate worse AHOs than previously reported and should be considered during pre-treatment counselling of PCa patients.

Background and purpose: A simulation-free approach, using the patient's diagnostic computed tomography (CT) for treatment planning, eliminates the need for a separate planning CT. Combined with conebeam computed tomography (CBCT)-guided online adaptive radiotherapy (oART), this strategy has the potential to create a more efficient treatment workflow and reduce the burden for the patients. The study aimed to evaluate the feasibility and time consumption of different simulation-free oART workflows for patients with metastatic spinal cord compression (MSCC) to identify the most suitable option for clinical implementation. Patient/material and methods: Diagnostic CT scans from patients diagnosed with MSCC were used for treatment planning, while CBCT scans from their first treatment session were retrospectively used to emulate the treatments. Four adaptive workflows were defined and assessed: Deformable Supervised (DefSup), Deformable Unsupervised (DefUn), Rigid Supervised (RigSup), and Rigid Unsupervised (RigUn). The supervised workflows involved manual corrections to the target structures, whereas the unsupervised workflows did not include any manual adjustments. Time stamps, segmentation quality, and dose plans were used to evaluate the feasibility of each workflow.

Results: A total of 120 simulation-free emulations were performed (based on 27 patients with 30 target sites). The DefSup workflow yielded the highest accuracy in both segmentation and dose distribution. Additionally, with a median time consumption of 6.57 min, this workflow demonstrates a level of reliability and quality suitable for clinical application.

Interpretation: The DefSup workflow was found to be the most optimal and safe for clinical implementation, as demonstrated by the successful treatment of the first patient with MSCC using this approach.

Background and purpose: Approximately 5-10% of cutaneous melanoma occurs in individuals with a family history of the disease. While known high-penetrance genes, such as CDKN2A, explain some cases, a substantial proportion of hereditary melanoma remains genetically undefined. Recently, germline variants in genes involved in telomere regulation, including POT1, TERT, ACD, and TERF2IP, have been identified in melanoma-prone families. This study investigated the prevalence and pathogenicity of POT1 variants in a Swedish familial melanoma cohort. Patient/material and methods: A total of 168 familial melanoma cases were screened for CDKN2A, CDK4, BAP1, and POT1. The population frequency of pathogenic variants (PVs) was assessed using the SweGen and the gnomAD databases. Functional evaluation was performed using a saturation genome editing (SGE) assay. Telomere length analysis was performed using quantitative polymerase chain reaction (qPCR) on blood-derived DNA from melanoma patients and healthy controls. The melanomas of the carriers were reviewed by expert dermatopathologists.

Results: Among the 161 CDKN2A/CDK4/BAP1-negative melanoma families included in this cohort, only one likely PV in POT1 (c.676C > A, p.His226Asn) was identified (0.6%). Population data confirmed its rarity. The carrier family exhibited multiple early-onset melanomas, with two out of three invasive cases displaying spitzoid morphology, and several other tumors. No significant telomere length differences were observed between carriers and controls. Two additional POT1 variants of uncertain significance were detected; both were predicted to be benign.

Interpretation: POT1 PVs were rare in the studied Swedish familial melanoma cases, implying limited contribution to hereditary melanoma in this population. Nonetheless, the identification of a previously unknown likely PV further supports the need for continued genetic screening in selected cases. POT1 testing should be considered in families with multiple melanomas, early onset and spitzoid histopathology, and co-occurring with other syndromic tumors.

Background and purpose: Dual-energy computed tomography (DECT) is increasingly used in radiotherapy delineation due to its enhanced soft tissue contrast. DECT also supports direct dose calculation. However, as most current DECT scanners allow for use in only certain body regions, conventional single-energy computed tomography (SECT) is still needed for some patients. A safe clinical introduction of DECT thus requires a combined workflow. This study therefore investigates whether a unified Hounsfield look-up table (HLUT) can be applied across SECT and DECT reconstructions. Patient/material and methods: A Gammex Advanced Electron Density phantom containing tissue-equivalent inserts was scanned using SECT (70-140 kVp and Sn100-Sn140 kVp, Sn meaning tin-filtered) and dual-spiral DECT to identify matching HLUTs for three SECT methods, including a standard reconstruction (only 120 kVp; Method 1), and kVp-independent reconstructions providing mass density (MD; Method 2) or relative electron density (RED; Method 3). Dose agreement was subsequently tested on two anthropomorphic phantoms. For each SECT method, DECT reconstructions were compared through voxel-wise analysis of computed tomography (CT) numbers, and by performing dose calculations in three anatomical regions: head, thorax, and abdomen/pelvis.

Results: Across all three SECT methods, DECT reconstructions with acceptable clinical CT number agreement were identified. Corresponding dose calculations between SECT- and DECT-based plans showed minimal differences.

Interpretation: This phantom study demonstrates that a unified HLUT can be applied across SECT and DECT using standard 120 kVp, MD, or RED reconstructions. This approach may streamline clinical workflows and support a safe and practical transition to DECT-based treatment planning.

Background and purpose: The aim of this study is to validate an Normal Tissue Complication Probability (NTCP) model for xerostomia in a large quality-registry cohort, enabling its future use in individualized NTCP-based treatment planning.

Material and methods: A model predicting grade ≥ 2 xerostomia (6 months post-radiotherapy) was selected for validation, including the mean dose to both the parotid and the submandibular glands, in addition to the baseline score for xerostomia, as predictors. Our local validation cohort consisted of 674 patients (204 events), treated between 2012 and 2024, with a median follow-up of 10.3 months (range 5-24). A closed testing procedure was performed to investigate the need for model updating, and the performance of the models was assessed with calibration curves, discrimination, the Brier score, and the Hosmer-Lemeshow test.

Results: The calibration curve demonstrated that the model predicted the dose-response relationship well. The validation cohort showed a slightly stronger dose response, with a slope of 1.16. The calibration intercept of -0.12 revealed an overestimation of xerostomia. However, the closed testing procedure indicated that a recalibration of the model was needed, and the HL-test showed a significant deviation. The recalibrated model showed perfect calibration but still limited discrimination (Area Under the Curve (AUC) 0.62).

Conclusion: The validated model performed well in our real-life dataset despite the differences between the training and validation cohorts, particularly considering the lack of baseline score in our cohort. This highlights the potential for improved performance with baseline inclusion but still suggests that an individualized NTCP-based treatment-planning protocol can be developed using the recalibrated published model.

p16-expression are implemented in the TNM8 classification of oropharyngeal cancer (OPSCC). Based on a nationwide cohort, we provide a detailed description of subsite variation in the age-standardised incidence-rates of OPSCC alongside an evaluation of the prognostic impact of p16-expression according to subsite after primary radiotherapy (RT). Patient/material and methods: A total of 8,462 Danish OPSCC patients from 1986 to 2020 were identified in the DAHANCA-database, and tumours were grouped into 'tonsil/base of tongue (BOT)', 'neighbouring subsites' and 'distant subsites'. Subsite-specific age-standardised incidence-rates were calculated, and outcome-analysis (loco-regional control, disease-free survival and overall-survival 5 years after the completion of RT) stratified by p16-status/subsite and restricted to curatively treated patients only (N = 3,387) was performed. Results: A 5-fold increase in the age-standardised incidence of OPSCC was observed and could be ascribed to the rise in p16-positive tumours of tonsil/BOT and neighbouring subsites only as neither the incidence rates nor the proportion of p16-positivity in distant subsites tumours changed over time. The prognostic impact of p16-status for all endpoints differed significantly across tumour subsites with the strongest association found in tonsil/BOT tumours, a diminishing but still significant impact in neighbouring subsite tumours and no significant impact in tumours arising in distant subsites. Interpretation: Our findings suggest that grouping all p16-positive OPSCC as one entity for staging and prognostication, as currently done in TNM8, is too simple as it does not accurately depict the differences in tumour biology and the consequent treatment response.