The Dutch-Belgian Registry of Stereotactic Body Radiation Therapy for Liver Metastases: Clinical Outcomes of 515 Patients and 668 Metastases.

PURPOSE: Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol. METHODS AND MATERIALS: A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium). All the centers had previously agreed on the items to be collected, the fractionation schemes, and the organs-at-risk constraints to be applied. Follow-up was performed at the discretion of the centers. Patient, tumor, and treatment characteristics were entered in the registry. Only liver metastases treated individually as independent targets and with at least 1 radiologic follow-up examination were considered for local control analysis. Toxicity of grade 3 or greater was scored according to the Common Terminology Criteria of Adverse Events (v4.03). RESULTS: Between January 1, 2013, and July 31, 2019, a total of 515 patients were entered in the web-based registry. The median age was 71 years. In total, 668 liver metastases were registered, and 447 were included for local control analysis. The most common primary tumor origin was colorectal cancer (80.3%), followed by lung cancer (8.9%) and breast cancer (4%). The most-used fractionation scheme was 3x18-20 Gy (36.0%), followed by 8x7.5 Gy (31.8%), 5x11-12 Gy (25.5%), and 12x5 Gy (6.7%). The median follow-up time was 1.1 years for local control and 2.3 years for survival. Actuarial 1-year local control was 87%; 1-year overall survival was 84%. Toxicity of grade 3 or greater was found in 3.9% of the patients. CONCLUSIONS: This multi-institutional study confirms the high rates of local control and limited toxicity in a large patient cohort. Stereotactic body radiation therapy should be considered a valuable part of the multidisciplinary approach to treating liver metastases.

Texture analysis of 3D dose distributions for predictive modelling of toxicity rates in radiotherapy.

BACKGROUND AND PURPOSE: To explore the use of texture analysis (TA) features of patients' 3D dose distributions to improve prediction modelling of treatment complication rates in prostate cancer radiotherapy. MATERIAL AND METHODS: Late toxicity scores, dose distributions, and non-treatment related (NTR) predictors for late toxicity, such as age and baseline symptoms, of 351 patients of the hypofractionation arm of the HYPRO randomized trial were used in this study. Apart from DVH parameters, also TA features of rectum and bladder 3D dose distributions were used for predictive modelling of gastrointestinal (GI) and genitourinary (GU) toxicities. Logistic Normal Tissue Complication Probability (NTCP) models were derived, using only NTR parameters, NTR + DVH, NTR + TA, and NTR + DVH + TA. RESULTS: For rectal bleeding, the area under the curve (AUC) for using only NTR parameters was 0.58, which increased to 0.68, and 0.73, when adding DVH or TA parameters respectively. For faecal incontinence, the AUC went up from 0.63 (NTR only), to 0.68 (+DVH) and 0.73 (+TA). For nocturia, adding TA features resulted in an AUC increase from 0.64 to 0.66, while no improvement was seen when including DVH parameters in the modelling. For urinary incontinence, the AUC improved from 0.68 to 0.71 (+DVH) and 0.73 (+TA). For GI, model improvements resulting from adding TA parameters to NTR instead of DVH were statistically significant (p < 0.04). CONCLUSION: Inclusion of 3D dosimetric texture analysis features in predictive modelling of GI and GU toxicity rates in prostate cancer radiotherapy improved prediction performance, which was statistically significant for GI.

Late toxicity in the randomized multicenter HYPRO trial for prostate cancer analyzed with automated treatment planning.

PURPOSE/OBJECTIVE: Assess to what extent the use of automated treatment planning would have reduced organ-at-risk dose delivery observed in the randomized HYPRO trial for prostate cancer, and estimate related toxicity reductions. Investigate to what extent improved plan quality for hypofractionation scheme as achieved with automated planning can potentially reduce observed enhanced toxicity for the investigated hypofractionation scheme to levels observed for conventional fractionation scheme. MATERIAL/METHODS: For 725 trial patients, VMAT plans were generated with an algorithm for automated multi-criterial plan generation (autoVMAT). All clinically delivered plans (CLINICAL), generated with commonly applied interactive trial-and-error planning were also available for the investigations. Analyses were based on dose-volume histograms (DVH) and predicted normal tissue complication probabilities (NTCP) for late gastrointestinal (GI) toxicity. RESULTS: Compared to CLINICAL, autoVMAT plans had similar or higher PTV coverage, while large and statistically significant OAR sparing was achieved. Mean doses in the rectum, anus and bladder were reduced by 7.8 ±â€¯4.7 Gy, 7.9 ±â€¯6.0 Gy and 4.2 ±â€¯2.9 Gy, respectively (p < 0.001). NTCPs for late grade ≥2 GI toxicity, rectal bleeding and stool incontinence were reduced from 23.3 ±â€¯9.1% to 19.7 ±â€¯8.9%, from 9.7 ±â€¯2.8% to 8.2 ±â€¯2.8%, and from 16.8 ±â€¯8.5% to 13.1 ±â€¯7.2%, respectively (p < 0.001). Reductions in rectal bleeding NTCP were observed for all published Equivalent Uniform Dose volume parameters, n. AutoVMAT allowed hypofractionation with predicted toxicity similar to conventional fractionation with CLINICAL plans. CONCLUSION: Compared to CLINICAL, autoVMAT had superior plan quality, with meaningful NTCP reductions for both conventional fractionation and hypofractionation schemes. AutoVMAT plans might reduce toxicity for hypofractionation to levels that were clinically observed (and accepted) for conventional fractionation. This may be relevant when considering clinical use of the investigated hypofractionation schedule with relatively high fraction dose (3.4 Gy).

Acute toxicity of the bowel after stereotactic robotic radiotherapy for abdominopelvic oligometastases.

AIM: To correlate dose-volume histogram (DVH) parameters with appearance of grade ≥2 acute and late gastrointestinal toxicity of stereotactic body radiotherapy (SBRT) in patients with abdominopelvic solitary or oligometastatic disease outside the liver. MATERIAL AND METHODS: Acute and late bowel toxicity of 84 abdominopelvic oligometastatic patients was registered. A logistic regression was performed between different DVH parameters and presence of grade ≥2 acute and late toxicity. A Normal Tissue Complication Probability (NTCP) model was built with significant parameters to determine complication probabilities (CP). RESULTS: Thirteen (15%) of 84 patients experienced of grade ≥2 acute toxicity, while 8 (10%) reported late toxicity complications. A significant relationship was found for EQD2 (V30Gy, V40Gy, V50Gy and V65Gy) and grade ≥2 acute toxicity. Dmax and D2 were not significant. Late grade ≥2 toxicity was not significantly correlated with any DVH parameter. According to our NTCP model for V40Gy, an irradiated bowel volume of 10 cm3 of V40Gy resulted in CP of grade ≥2 acute toxicity of less than 10%. Local control was 87% at 2 years and 82% at 5 years. Overall survival was 61% at 2 years and 32% at 5 years. CONCLUSIONS: After SBRT for abdominopelvic oligometastases, in general, the presence of acute and late toxicity was low. A significant relationship was found for V30Gy, V40Gy, V50Gy and V65Gy and grade ≥2 acute toxicity. We estimated acute complication probabilities per volume of irradiated bowel by V40Gy and V50Gy.

Intra-patient semi-automated segmentation of the cervix-uterus in CT-images for adaptive radiotherapy of cervical cancer.

For online adaptive radiotherapy of cervical cancer, fast and accurate image segmentation is required to facilitate daily treatment adaptation. Our aim was twofold: (1) to test and compare three intra-patient automated segmentation methods for the cervix-uterus structure in CT-images and (2) to improve the segmentation accuracy by including prior knowledge on the daily bladder volume or on the daily coordinates of implanted fiducial markers. The tested methods were: shape deformation (SD) and atlas-based segmentation (ABAS) using two non-rigid registration methods: demons and a hierarchical algorithm. Tests on 102 CT-scans of 13 patients demonstrated that the segmentation accuracy significantly increased by including the bladder volume predicted with a simple 1D model based on a manually defined bladder top. Moreover, manually identified implanted fiducial markers significantly improved the accuracy of the SD method. For patients with large cervix-uterus volume regression, the use of CT-data acquired toward the end of the treatment was required to improve segmentation accuracy. Including prior knowledge, the segmentation results of SD (Dice similarity coefficient 85 ± 6%, error margin 2.2 ± 2.3 mm, average time around 1 min) and of ABAS using hierarchical non-rigid registration (Dice 82 ± 10%, error margin 3.1 ± 2.3 mm, average time around 30 s) support their use for image guided online adaptive radiotherapy of cervical cancer.