Treatment planning for patients with low rectal cancer in a multicenter prospective organ preservation study.

BACKGROUND: Non-surgical management of rectal cancer relies on (chemo)radiotherapy as the definitive treatment modality. This study reports and evaluates the clinical high dose radiotherapy treatment plans delivered to patients with low resectable rectal cancer in a Danish multicenter trial. METHODS: The Danish prospective multicenter phase II Watchful Waiting 2 trial (NCT02438839) investigated definitive chemoradiation for non-surgical management of low rectal cancer. Three Danish centers participated in the trial and committed to protocol-specified treatment planning and delivery requirements. The protocol specified a dose of 50.4 Gy in 28 fractions to the elective volume (CTV-/PTV-E) and a concomitant boost of 62 Gy in 28 fractions to the primary target volume (CTV-/PTV-T). RESULTS: The trial included 108 patients, of which 106 treatment plans were available for retrospective analysis. Dose coverage planning goals for the main target structures were fulfilled for 94% of the treatment plans. However, large intercenter differences in doses to organs-at-risk (OARs) were seen, especially for the intestines. Five patients had a V60Gy>10 cm3 for the intestines and two patients for the bladder. CONCLUSION: Prescribed planning goals for target coverage were fulfilled for 94% of the treatment plans, however analysis of OAR doses and volumes indicated intercenter variations. Dose escalation to 62 Gy (as a concomitant boost to the primary tumor) introduced no substantial high dose volumes (>60 Gy) to the bladder and intestines. The treatment planning goals may be used for future prospective evaluation of highdose radiotherapy for organ preservation for low rectal cancer.

Geometric distortions in clinical MRI sequences for radiotherapy: insights gained from a multicenter investigation.

BACKGROUND: As magnetic resonance imaging (MRI) becomes increasingly integrated into radiotherapy (RT) for enhanced treatment planning and adaptation, the inherent geometric distortion in acquired MR images pose a potential challenge to treatment accuracy. This study aimed to evaluate the geometric distortion levels in the clinical MRI protocols used across Danish RT centers and discuss influence of specific sequence parameters. Based on the variety in geometric performance across centers, we assess if harmonization of MRI sequences is a relevant measure. MATERIALS AND METHODS: Nine centers participated with 12 MRI scanners and MRI-Linacs (MRL). Using a travelling phantom approach, a reference MRI sequence was used to assess variation in baseline distortion level between scanners. The phantom was also scanned with local clinical MRI sequences for brain, head/neck (H/N), abdomen, and pelvis. The influence of echo time, receiver bandwidth, image weighting, and 2D/3D acquisition was investigated. RESULTS: We found a large variation in geometric accuracy across 93 clinical sequences examined, exceeding the baseline variation found between MRI scanners (σ = 0.22 mm), except for abdominal sequences where the variation was lower. Brain and abdominal sequences showed lowest distortion levels ([0.22, 2.26] mm), and a large variation in performance was found for H/N and pelvic sequences ([0.19, 4.07] mm). Post hoc analyses revealed that distortion levels decreased with increasing bandwidth and a less clear increase in distortion levels with increasing echo time. 3D MRI sequences had lower distortion levels than 2D (median of 1.10 and 2.10 mm, respectively), and in DWI sequences, the echo-planar imaging read-out resulted in highest distortion levels. CONCLUSION: There is a large variation in the geometric distortion levels of clinical MRI sequences across Danish RT centers, and between anatomical sites. The large variation observed makes harmonization of MRI sequences across institutions and adoption of practices from well-performing anatomical sites, a relevant measure within RT.

A national repository of complete radiotherapy plans: design, Results, and experiences.

BACKGROUND: Previously, many radiotherapy (RT) trials were based on a few selected dose measures. Many research questions, however, rely on access to the complete dose information. To support such access, a national RT plan database was created. The system focuses on data security, ease of use, and re-use of data. This article reports on the development and structure, and the functionality and experience of this national database. METHODS AND MATERIALS: A system based on the DICOM-RT standard, DcmCollab, was implemented with direct connections to all Danish RT centres. Data is segregated into any number of collaboration projects. User access to the system is provided through a web interface. The database has a finely defined access permission model to support legal requirements. RESULTS: Currently, data for more than 14,000 patients have been submitted to the system, and more than 50 research projects are registered. The system is used for data collection, trial quality assurance, and audit data set generation.Users reported that the process of submitting data, waiting for it to be processed, and then manually attaching it to a project was resource intensive. This was accommodated with the introduction of triggering features, eliminating much of the need for users to manage data manually. Many other features, including structure name mapping, RT plan viewer, and the Audit Tool were developed based on user input. CONCLUSION: The DcmCollab system has provided an efficient means to collect and access complete datasets for multi-centre RT research. This stands in contrast with previous methods of collecting RT data in multi-centre settings, where only singular data points were manually reported. To accommodate the evolving legal environment, DcmCollab has been defined as a 'data processor', meaning that it is a tool for other research projects to use rather than a research project in and of itself.

End-to-end framework for automated collection of large multicentre radiotherapy datasets demonstrated in a Danish Breast Cancer Group cohort.

Large Digital Imaging and Communications in Medicine (DICOM) datasets are key to support research and the development of machine learning technology in radiotherapy (RT). However, the tools for multi-centre data collection, curation and standardisation are not readily available. Automated batch DICOM export solutions were demonstrated for a multicentre setup. A Python solution, Collaborative DICOM analysis for RT (CORDIAL-RT) was developed for curation, standardisation, and analysis of the collected data. The setup was demonstrated in the DBCG RT-Nation study, where 86% (n = 7748) of treatments in the inclusion period were collected and quality assured, supporting the applicability of the end-to-end framework.

Patient-reported lower limb edema after primary radiotherapy for prostate cancer.

BACKGROUND: Secondary lymphedema is a known side effect to radiotherapy (RT), but limited information regarding prevalence and risk factors for lower limb edema (LLE) after curative radiotherapy in patients with prostate cancer (PCa) is available. This study provides a descriptive analysis of patient-reported LLE with analysis of risk factors in a cohort of patients with PCa treated with curative RT. MATERIAL AND METHODS: A total of 302 patients with PCa with prospective registration of patient-reported LLE (EORTC QLQ-PR25 (Question 46)) were included. Analysis of LLE was done with the calculation of prevalence rates and Kaplan-Meier statistics. Risk factors for LLE were analyzed multivariate with Cox regression analysis. RESULTS: At a median follow-up of 15 (3-51) months, the overall crude incidence of patients reporting 'quite a bit' or 'a lot' of LLE was 49 (16.2%) and 21 (7.0%), respectively. The baseline prevalence rate of 'quite a bit' and 'a lot' of LLE was 5.0% and 0.8%, respectively. During follow-up the prevalence rate for 'quite a bit' or 'a lot' of LLE increased significantly and remained constant from 6 months where 11.5% (±1.7%) reported 'quite a bit' and 2.9% (±0.5%) reported 'very much' LLE (p < 0.001), respectively.Significant risk factors (p < 0.10) for LLE in univariate analysis included lymph node irradiation (HR:2.325), baseline Body Mass Index (BMI) (HR:1.100), Charlson Comorbidity Index (HR:1.227), Androgen Deprivation Therapy (HR:2,979), and Performance Status (HR:0.594). Only high BMI (HR:1.091) remained significant in multivariate analysis with a three-fold increase in LLE in patients with BMI ≥ 30 compared to normal weight patients. CONCLUSION: Severe patient-reported LLE after curative RT for PCa is rare. Significantly more patients with a high BMI report 'quite a bit' or 'very much' LLE compared to patients with a normal BMI. Obese PCa patients could be offered a rehabilitation program for early detection and management of LLE.

Robust extraction of biological information from diffusion-weighted magnetic resonance imaging during radiotherapy using semi-automatic delineation.

Background and purpose: Diffusion-Weighted Magnetic Resonance imaging (DWI) quantifies water mobility through the Apparent Diffusion Coefficient (ADC), a promising radiotherapy response biomarker. ADC measurements depend on manual delineation of a region of interest, a time-consuming and observer-dependent process. Here, the aim was to introduce and test the performance of a new, semi-automatic delineation tool (SADT) for ADC calculation within the viable region of the tumour. Materials and methods: Thirty patients with rectal cancer were scanned with DWI before radiotherapy (RT) (baseline) and two weeks into RT (week 2). The SADT was based on intensities in b=1100 s mm-2 DWI and derived ADC maps. ADC values measured using the SADT and manual delineations were compared using Bland-Altman- and correlation analyses. Delineations were repeated to assess intra-observer variation, and repeatability was estimated using repeated DWI scans. Results: ADC measured using the SADT and manual delineation showed strong and moderate correlation at baseline and week 2, respectively, with the SADT measuring systematically smaller values. Intra-observer ADC variation was slightly smaller for the SADT compared to manual delineation both at baseline, [-0.00; 0.03] vs. [-0.02; 0.04] 10-3 mm2 s-1, and week 2, [-0.01; 0.00] vs. [-0.04; 0.07] 10-3 mm2 s-1 (68.3% limits of agreement). The ADC change between baseline and week 2 was larger than the ADC uncertainty ( ± 0.04 · 10-3 mm2 s-1) in all cases except one. Conclusion: The presented SADT showed performance comparable to manual expert delineation, and with sufficient consistency to allow extraction of potential biological information from the viable tumour.

Selection criteria for early breast cancer patients in the DBCG proton trial - The randomised phase III trial strategy.

BACKGROUND AND PURPOSE: Adjuvant radiotherapy of internal mammary nodes (IMN) improves survival in high-risk early breast cancer patients but inevitably leads to more dose to heart and lung. Target coverage is often compromised to meet heart/lung dose constraints. We estimate heart and lung dose when target coverage is not compromised in consecutive patients. These estimates are used to guide the choice of selection criteria for the randomised Danish Breast Cancer Group (DBCG) Proton Trial. MATERIALS AND METHODS: 179 breast cancer patients already treated with loco-regional IMN radiotherapy from 18 European departments were included. If the clinically delivered treatment plan did not comply with defined target coverage requirements, the plan was modified retrospectively until sufficient coverage was reached. The choice of selection criteria was based on the estimated number of eligible patients for different heart and lung dose thresholds in combination with proton therapy capacity limitations and dose-response relationships for heart and lung. RESULTS: Median mean heart dose was 3.0 Gy (range, 1.1-8.2 Gy) for left-sided and 1.4 Gy (0.4-11.5 Gy) for right-sided treatment plans. Median V17Gy/V20Gy (hypofractionated/normofractionated plans) for ipsilateral lung was 31% (9-57%). The DBCG Radiotherapy Committee chose mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37% as thresholds for inclusion in the randomised trial. Using these thresholds, we estimate that 22% of patients requiring loco-regional IMN radiotherapy will be eligible for the trial. CONCLUSION: The patient selection criteria for the DBCG Proton Trial are mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37%.

Stability of radiomic features of apparent diffusion coefficient (ADC) maps for locally advanced rectal cancer in response to image pre-processing.

Quantitative imaging features (radiomics) extracted from apparent diffusion coefficient (ADC) maps of rectal cancer patients can provide additional information to support treatment decision. Most available radiomic computational packages allow extraction of hundreds to thousands of features. However, two major factors can influence the reproducibility of radiomic features: interobserver variability, and imaging filtering applied prior to features extraction. In this exploratory study we seek to determine to what extent various commonly-used features are reproducible with regards to the mentioned factors using ADC maps from two different clinics (56 patients). Features derived from intensity distribution histograms are less sensitive to manual tumour delineation differences, noise in ADC images, pixel size resampling and intensity discretization. Shape features appear to be strongly affected by delineation quality. On the whole, textural features appear to be poorly or moderately reproducible with respect to the image pre-processing perturbations we reproduced.

Elastography and diffusion-weighted MRI in patients with testicular microlithiasis, normal testicular tissue, and testicular cancer: an observational study.

BACKGROUND: Ultrasound elastography is increasingly available in clinical practice. Recent studies showed higher velocity stiffness in testicular tumors compared to normal testicles. PURPOSE: To evaluate ultrasound elastography in combination with the apparent diffusion coefficient measurements in diffusion weighted (DW) magnetic resonance imaging (MRI) in testicles. DW can be a useful tool in evaluating testicular malignancies. However, the relationship between velocity stiffness and MRI diffusion is not well established. MATERIAL AND METHODS: We prospectively included 132 patients with testicular microlithiasis (n = 53), or normal testicular tissue (n = 53), or suspected for testicular cancer (n = 26). All 132 patients underwent ultrasonography including shear wave elastography and MRI diffusion coefficient examination of the scrotum. RESULTS: No clinically relevant difference in velocity stiffness was found between normal and testicles with microlithiasis. There was a significant difference in stiffness between patients with testicular microlithiasis (0.78 m/s), normal testicular tissue (0.77 m/s), and patients with testicular cancer (1.95 m/s) ( P ≤ 0.001). Similarly, there was a statistically significant difference in MRI diffusion values between patients with testicular microlithiasis (0.978 × 10-3 mm2 s-1), normal testicular tissue (0.929 × 10-3 mm2 s-1), and testicular cancers (0.743 × 10-3 mm2 s-1) ( P < 0.01). CONCLUSION: Patients with testicular microlithiasis had no malignant characteristics measured with shear wave elastography or MRI diffusion. MRI diffusion and elastography may be useful to preoperatively differentiate benign from malignant testicular lesions.