Time-resolved clinical dose volume metrics, calculations and predictions based on source tracking measurements and uncertainties to aid treatment verification and error detection for HDR brachytherapy-a proof-of-principle study.

Objective.High-dose-rate (HDR) brachytherapy lacks routinely available treatment verification methods. Real-time tracking of the radiation source during HDR brachytherapy can enhance treatment verification capabilities. Recent developments in source tracking allow for measurement of dwell times and source positions with high accuracy. However, more clinically relevant information, such as dose discrepancies, is still needed. To address this, a real-time dose calculation implementation was developed to provide more relevant information from source tracking data. A proof-of-principle of the developed tool was shown using source tracking data obtained from a 3D-printed anthropomorphic phantom.Approach.Software was developed to calculate dose-volume-histograms (DVH) and clinical dose metrics from experimental HDR prostate treatment source tracking data, measured in a realistic pelvic phantom. Uncertainty estimation was performed using repeat measurements to assess the inherent dose measuring uncertainty of thein vivodosimetry (IVD) system. Using a novel approach, the measurement uncertainty can be incorporated in the dose calculation, and used for evaluation of cumulative dose and clinical dose-volume metrics after every dwell position, enabling real-time treatment verification.Main results.The dose calculated from source tracking measurements aligned with the generated uncertainty bands, validating the approach. Simulated shifts of 3 mm in 5/17 needles in a single plan caused DVH deviations beyond the uncertainty bands, indicating errors occurred during treatment. Clinical dose-volume metrics could be monitored in a time-resolved approach, enabling early detection of treatment plan deviations and prediction of their impact on the final dose that will be delivered in real-time.Significance.Integrating dose calculation with source tracking enhances the clinical relevance of IVD methods. Phantom measurements show that the developed tool aids in tracking treatment progress, detecting errors in real-time and post-treatment evaluation. In addition, it could be used to define patient-specific action limits and error thresholds, while taking the uncertainty of the measurement system into consideration.

Endorectal contact radiation boosting: Making the case for dose AND volume reporting.

INTRODUCTION: The various rectal endoluminal radiation techniques all have steep, but different, dose gradients. In rectal contact brachytherapy (CXB) doses are typically prescribed and reported to the applicator surface and not to the gross tumor volume (GTV), clinical target volume (CTV) or organs at risk (OAR), which is crucial to understand tumor response and toxicity rates. To quantify the above-described problem, we performed a dose modeling study using a fixed prescription dose at the surface of the applicator and varied tumor response scenarios. METHODS: Endorectal ultrasound-based 3D-volume-models of rectal tumors and the rectal wall were used to simulate the delivered dose to GTV, CTV and the rectal wall layers, assuming treatment with Maastro HDR contact applicator for rectal cancer with a fixed prescription dose to the applicator surface (equivalent to 3 × 30 Gy CXB) and various response scenarios. RESULTS: An identical prescribed dose to the surface of the applicator resulted in a broad range of doses delivered to the GTV, CTV and the uninvolved intestinal wall. For example, the equieffective dose in 2 Gy per fraction (EQD2) D90% of the GTV varied between 63 and 231 Gy, whereas the EQD2 D2cc of the rectal wall varied between 97 and 165 Gy. CONCLUSION: Doses prescribed at the surface are not representative of the dose received by the tumor and the bowel wall. This stresses the relevance of dose reporting and prescription to GTV and CTV volumes and OAR in order to gain insight between delivered dose, local control and toxicity and to optimize treatment protocols.

Validation of the collapsed cone algorithm for HDR liver brachytherapy against Monte Carlo simulations.

PURPOSE: To validate the collapsed cone (CC) algorithm against Monte Carlo (MC) simulations for model-based dose calculations in high-dose-rate (HDR) liver brachytherapy. METHODS AND MATERIALS: Doses for liver brachytherapy treatment plans of 10 cases were retrospectively recalculated with a model-based approach using Monte Carlo n-Particle Code (MCNP) 6 (Dm,m-MC) and Oncentra Brachy ACE (Dm,m-ACE). Tissue segmentation consisted of assigning uniform compositions and mass densities to predefined Hounsfield Unit (HU) thresholds. Resulting doses were compared according to dose volume histogram parameters typical for clinical routine. These included the percentage liver volume receiving 5 Gy (V5Gy) or 10 Gy (V10Gy), the maximum dose to one cubic centimeter (D1cc) of organs at risk, the clinical target volume (CTV) fractions receiving 150% (V150), 100% (V100), 95% (V95) and 90% (V90) of the prescribed dose and the absolute doses to 95% (D95) and 90% (D90) of the CTV volumes. RESULTS: Doses from Oncentra Brachy ACE agreed well with MC simulations. Differences were seen far from the source, in low-density regions and bone structures. Median percentage deviations were 1.1% for the liver V5Gy and 0.4% for the liver V10Gy, with deviations of largest magnitude amounting to 2.2% and 1.0%, respectively. Organs at risk had median deviations ranging from 0.3% to 1.5% for D1cc, with outliers ranging up to 4.6%. CTV volume parameter deviations ranged between -1.5% and 0.5%, dose parameter deviations ranged mostly between -2% and 1%, with two outliers at -4.0% and -3.4% for a small CTV.

In vivo dosimetry in external beam photon radiotherapy: Requirements and future directions for research, development, and clinical practice.

External beam radiotherapy with photon beams is a highly accurate treatment modality, but requires extensive quality assurance programs to confirm that radiation therapy will be or was administered appropriately. In vivo dosimetry (IVD) is an essential element of modern radiation therapy because it provides the ability to catch treatment delivery errors, assist in treatment adaptation, and record the actual dose delivered to the patient. However, for various reasons, its clinical implementation has been slow and limited. The purpose of this report is to stimulate the wider use of IVD for external beam radiotherapy, and in particular of systems using electronic portal imaging devices (EPIDs). After documenting the current IVD methods, this report provides detailed software, hardware and system requirements for in vivo EPID dosimetry systems in order to help in bridging the current vendor-user gap. The report also outlines directions for further development and research. In vivo EPID dosimetry vendors, in collaboration with users across multiple institutions, are requested to improve the understanding and reduce the uncertainties of the system and to help in the determination of optimal action limits for error detection. Finally, the report recommends that automation of all aspects of IVD is needed to help facilitate clinical adoption, including automation of image acquisition, analysis, result interpretation, and reporting/documentation. With the guidance of this report, it is hoped that widespread clinical use of IVD will be significantly accelerated.

Microscopic intramural extension of rectal cancer after neoadjuvant chemoradiation: A meta-analysis based on individual patient data.

OBJECTIVE: In selected rectal cancer patients with residual local disease following neoadjuvant chemoradiation (CRT) and the preference of an organ preservation pathway, additional treatment with dose escalation by endoluminal radiotherapy (RT) may ultimately result in a clinical complete response. To date, the widespread introduction of selective endoluminal radiation techniques is hampered by a lack of evidence-based guidelines that describe the radiation treatment volume in relation to the residual tumor mass. In order to convert an incomplete response into a complete one with additional treatment such as dose-escalation with endoluminal RT from a theoretical perspective, it seems important to treat all remaining microscopic tumor cells after CRT. In this setting, residual tumor extension beneath normal appearing mucosa (microscopic intramural spread - MIS) becomes relevant for accurate tumor volume and margin estimation. With the goal of providing evidence-based guidelines that define an appropriate treatment volume and patient selection, we present results from a meta-analysis based on individual patient data of studies that have assessed the extent or range of MIS of rectal cancers after neoadjuvant CRT. This meta-analysis should provide an estimate of the residual tumor volume/extension that needs to be targeted by any additional radiation therapy boost in order to achieve complete tumor eradication after initial incomplete or near-complete response following standard CRT. METHODS AND MATERIALS: A PubMed search was performed. Additional articles were selected based on identification from reference lists. Papers were eligible when reporting MIS in patients who were treated by total mesorectal excision or local excision/transanal endoscopic microsurgery (TEM) after neo-adjuvant long-course CRT. The mean MIS was calculated for the entire group along with the 70th until 95th percentiles. Additional exploratory subgroup analyses were performed. RESULTS: Individual patient data from 349 patients with residual disease from five studies were analyzed. 80% of tumors showed no MIS. In order to appropriately treat MIS in 95% of rectal cancer patients after CRT, a margin of 5.5 mm around the macroscopic tumor would suffice. An exploratory subgroup analysis showed that T-stage after CRT (ypT) and time interval between neoadjuvant CRT and surgery are significant factors predicting the extent of MIS (p < 0.001.) The group of ypT1 had the smallest MIS, followed by the ypT3-4 group, while the ypT2 group had the largest MIS (p < 0.001). Regarding time interval between CRT and surgery, a statistically significant difference was seen when comparing the three time-interval groups (less than 8 weeks, 8-12 weeks, and more than 12 weeks), where waiting more than 12 weeks after CRT resulted in the largest MIS (p < 0.0001). CONCLUSION: Based on this meta-analysis, in order to treat the MIS for 95% of rectal cancer patients after CRT, a Clinical Target Volume (CTV) margin of 5.5 mm from the lateral most edge of the macroscopic tumor would suffice. 80% of tumors showed no MIS and would not require an extra CTV margin for treatment. These findings support the feasibility of localized radiotherapy boosts for dose-escalation to improve response among patients with incomplete response after standard CRT and can also be applied in the surgical setting.