Empirical analysis of a plan-of-the-day strategy to approximate daily online reoptimization for prostate CBCT-guided adaptive radiotherapy.

PURPOSE: Adaptive radiotherapy (ART) can improve the dose delivered to the patient in the presence of anatomic variations. However, the required time, effort, and clinical resources are intensive. This work analyzed a plan-of-the-day (POD) approach on clinical patients treated with online ART to explore implementations that balance dosimetric benefit and clinical resource cost. METHODS: Eight patients treated to the prostate and proximal seminal vesicles with 26 fractions of CBCT-guided, daily online ART were retrospectively analyzed. With a plan library composed of daily adaptive plans from the initial week of treatment and the original plan, the effect of a POD approach starting the following week was investigated by simulating use of these previously generated plans under 3- and 6-degree-of-freedom patient alignment. The plan selected for each treatment was that from the library that maximized the Dice similarity coefficient of the clinical target volume with that of the current treatment fraction. The resulting distribution of several target coverage and organ-at-risk dose metrics are described relative to those achieved with the daily online reoptimized adaptive technique. RESULTS: The values of target coverage and organ-at-risk dose metrics varied across patients and metrics. The POD schemas closely approximated the reference values from a fully reoptimized adaptive plan yet required less than 20% of the reoptimization effort. The POD schemas also had a much greater effect on target coverage metrics than 6-degree-of-freedom registration did. Organ-at-risk dose metrics also varied considerably across patients but did not exhibit a consistent dependence on the particular schema. CONCLUSIONS: POD schemas were able to achieve the vast majority of the dosimetric benefit of daily online ART with a small fraction of the online reoptimization effort. Strategies like this might allow for more practical and strategic implementation of ART so as to benefit a greater number of patients.

Triggering daily online adaptive radiotherapy in the pelvis: Dosimetric effects and procedural implications of trigger parameter-value selection.

BACKGROUND: Online adaptive radiotherapy (ART) can address dosimetric consequences of variations in anatomy by creating a new plan during treatment. However, ART is time- and labor-intensive and should be implemented in a resource-conscious way. Adaptive triggers composed of parameter-value pairs may direct the judicious use of online ART. PURPOSE: This work analyzed our clinical experience using CBCT-based daily online ART to demonstrate how a conceptual framework based on adaptive triggers affects the dosimetric and procedural impact of ART. METHODS: Sixteen patients across several pelvic sites were treated with CBCT-based daily online ART. Differences in standardized dose metrics were compared between the original plan, the original plan recalculated on the daily anatomy, and an adaptive plan. For each metric, trigger values were analyzed in terms of the proportion of treatments adapted and the distribution of metric values. RESULTS: Target coverage metrics were compromised due to anatomic variation with the average change per treatment ranging from -0.90 to -0.05 Gy, -0.47 to -0.02 Gy, -0.31 to -0.01 Gy, and -12.45% to -2.65% for PTV D99%, PTV D95%, CTV D99%, and CTV V100%, respectively. These were improved using the adaptive plan (-0.03 to 0.01 Gy, -0.02 to 0.00 Gy, -0.03 to 0.00 Gy, and -4.70% to 0.00%, respectively). Increasingly strict triggers resulted in a non-linear increase in the proportion of treatments adapted and improved the distribution of metric values with diminishing returns. Some organ-at-risk (OAR) metrics were compromised by anatomic variation and improved using the adaptive plan, but changes in most OAR metrics were randomly distributed. CONCLUSIONS: Daily online ART improved target coverage across multiple pelvic treatment sites and techniques. These effects were larger than those for OAR metrics, suggesting that maintaining target coverage was our primary benefit of CBCT-based daily online ART. Analyses like these can determine online ART triggers from a cost-benefit perspective.

Rodent Model of Brain Radionecrosis Using Clinical LINAC-Based Stereotactic Radiosurgery.

Purpose: Our purpose was to develop a rodent model of brain radionecrosis using clinical linear accelerator based stereotactic radiosurgery. Methods and Materials: Single fraction maximum prescription points in the mouse's left hemisphere were irradiated using linear accelerator-based stereotactic radiosurgery with multiple arcs at 60 (n = 5), 100 (n = 5), and 140 (n = 5) Gy. Rats (n = 6) were similarly treated with 140 Gy. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) was used to track radiation injury in mice over weeks (100 and 140 Gy) or months (60 Gy). Target accuracy was measured by the distance from the prescription point to the center of the earliest Gd-MRI enhancement. Confirmation of necrosis via histology was performed at the subject endpoints. Results: Radiation injury as indicated by Gd-MRI was first identified at 2 weeks (140 Gy), 4 to 6 weeks (100 Gy), and 8 months (60 Gy). A volumetric time course showed rapid growth in the volume of Gd-MRI signal enhancement after the appearance of apparent necrosis. Histopathologic features were consistent with radionecrosis. Conclusions: The presented method uses a commonly available clinical linear accelerator to induce radiation necrosis in both mice and rats. The treatment is modeled after patient therapy for a more direct model of human tissue under a range of doses used in clinical neuro-ablation techniques. The short time to onset of apparent necrosis, accurate targeting of the prescription point, high incidence of necrosis, and similar pathologic features make this a suitable animal model for further research in radionecrosis.

Effects of cone versus multi-leaf collimation on dosimetry and neurotoxicity in patients with small arteriovenous malformations treated by stereotactic radiosurgery.

PURPOSE/OBJECTIVE: Linear accelerator (LINAC) based stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) is delivered with cone or multileaf collimators (MLCs), and favorable dosimetry is associated with reduced radionecrosis in normal brain tissue. This study aims to determine whether cones or MLCs has better dosimetric characteristics, to predict differences in toxicity. METHODS: All patients treated for AVMs using LINAC SRS from 2003-2017 were examined retrospectively. Demographic data, volumes of normal tissue exposed to 12Gy (V12Gy[cc]) and 4Gy (V4Gy[cc]), maximal dose, and dose gradient were analyzed. Univariate and multivariate analyses were used to evaluate relationships between collimator type, dosimetric parameters, and toxicity. Propensity score matching was used to adjust for AVM size. RESULTS: Compared to MLC, cones were independently associated with reduced V12Gy[cc] after propensity score matching (p=0.008) and reduced neurotoxicity (p=0.016). Higher V12Gy[cc] (p=0.0008) and V4Gy[cc] (p=0.002) were associated with increased neurotoxicity. CONCLUSIONS: Treating AVMs with cone-based SRS over MLC-based SRS may improve dosimetry and reduce toxicities.

Comparison of pretreatment VMAT quality assurance with the integral quality monitor (IQM) and electronic portal imaging device (EPID).

The purpose of this study was to compare pretreatment volumetric modulated arc therapy (VMAT) quality assurance (QA) measurements and evaluate the multileaf collimator (MLC) error sensitivity of two detectors: the integral quality monitor (IQM) system (iRT systems IQM) and the electronic portal imaging device (EPID) (Varian PortalVision aS1200). Pretreatment QA measurements were performed for 20 retrospective VMAT plans (53 arcs). A subset of ten plans (23 arcs) was used to investigate MLC error sensitivity of each device. Eight MLC error plans were created for each VMAT plan. The errors included systematic opening/closing (±0.25, ±0.50, ±0.75 mm) of the MLC and random positional errors (1 mm) for individual/groups of leaves. The IQM was evaluated using the percent error of the measured cumulative signal relative to the calculated signal. The EPID was evaluated using two methods: a novel percent error of the measured relative to the predicted cumulative signals, and gamma (γ) analysis (1%/1 mm, 2%/2 mm, 3%/3 mm and 3%/1 mm for Stereotactic Body Radiation Therapy plans). The average change in maximum dose obtained from dose-volume histogram (DVH) data and change in detector signals for different systematic MLC shifts was also compared. Cumulative signal differences showed similar levels of agreement between measured and expected detector signals (IQM: 1.00 ± 0.55%; EPID: 1.22 ± 0.92%). Results from γ analysis lacked specificity. Only the 1%/1 mm criteria produced data with remarkable differences. A strong linear correlation was observed between IQM and EPID cumulative signal differences with MLC error magnitude (R = 0.99). Likewise, results indicate a strong correlation between the cumulative signal for both detectors and DVH dose (RIQM  = 0.99; REPID  = 0.97). In conclusion, use of cumulative signal differences could be more useful for detecting errors in treatment delivery in EPID than γ analysis.

Postoperative Fractionated Stereotactic Radiosurgery to the Tumor Bed for Surgically Resected Brain Metastases.

Introduction Stereotactic radiosurgery (SRS) is increasingly used as an alternative to whole brain radiotherapy (WBRT) following surgical resection of brain metastases. We analyzed the outcomes of postoperative frameless fractionated stereotactic radiosurgery (fSRS) cases for surgically resected brain metastases at our institution. Materials and Methods We performed a retrospective review of 85 patients who underwent fSRS to 87 resection beds from 2006 - 2014 with a median follow-up of 6.4 months. Clinically relevant outcomes were assessed with analysis to determine predictors of these outcomes. Results The median target volume was 9.8 cm-3 (1.1 - 43.1 cm-3). The most frequently used fractionation scheme was 3,000 cGy in five fractions. The rates of local control (LC), distant brain failure (DBF), and overall survival (OS) at one-year were 87%, 52%, and 52%, respectively. Five patients (5.9%) experienced Grade >2 toxicity related to fSRS, including seizures (two), symptomatic radionecrosis (two), and potential treatment-related death (one). A multivariable analysis revealed that tumor volume (p < 0.001) and number of fractions (p < 0.001) were associated with LC, while recursive partitioning analysis (RPA) class (p < .0001), tumor volume (p = .0181), and the number of fractions (p = .0181) were associated with OS. Conclusions Postoperative fSRS for surgically resected brain metastases is well-tolerated and achieves durable LC. Further studies are needed to determine the optimal dose and fractionation for fSRS as well as to compare outcomes with WBRT.

Margin of error for a frameless image guided radiosurgery system: Direct confirmation based on posttreatment MRI scans.

PURPOSE: To report on radiosurgery delivery positioning accuracy in the treatment of tremor patients with frameless image guided radiosurgery using the linear accelerator (LINAC) based ExacTrac system and to describe quality assurance (QA) procedures used. METHODS AND MATERIALS: Between 2010 and 2015, 20 patients underwent radiosurgical thalamotomy targeting the ventral intermediate nucleus for the treatment of severe tremor. The median prescription dose was 140 Gy (range, 120-145 Gy) in a single fraction. The median maximum dose was 156 Gy (range, 136-162 Gy). All treatment planning was performed with the iPlan system using a 4-mm circular cone with multiple arcs. Before each treatment, QA procedures were performed, including the imaging system. As a result of the extremely high dose delivered in a single fraction, a well-defined circular mark developed on the posttreatment magnetic resonance imaging (MRI). Eight of these 20 patients were selected to evaluate treatment localization errors because their circular marks were available in posttreatment MRI. In this study, the localization error is defined as the distance between the center of the intended target and the center of the posttreatment mark. RESULTS: The mean error of distance was found to be 1.1 mm (range, 0.4-1.5 mm). The mean errors for the left-right, anteroposterior, and superoinferior directions are 0.5 mm, 0.6 mm, and 0.7 mm, respectively. CONCLUSIONS: The result reported in this study includes all tremor patients treated at our institution when their posttreatment MRI data were available for study. It represents a direct confirmation of target positioning accuracy in radiosurgery with a LINAC-based frameless system and its limitations. This level of accuracy is only achievable with an appropriate QA program in place for a LINAC-based frameless radiosurgery system.

Does radiation dose to the vestibule predict change in balance function and patient perceived dizziness following stereotactic radiotherapy for vestibular schwannoma?

OBJECTIVE: To date, the majority of the vestibular schwannoma (VS) literature has focused on tumor control rates, facial nerve function and hearing preservation. Other factors that have been shown to significantly affect quality-of-life (QOL), such as dizziness, remain understudied. The primary objective of the current study is to investigate the association between radiation dose to the vestibule and post-treatment changes in vestibular function and patient reported dizziness handicap. MATERIALS AND METHODS: This is a prospective observational pilot study at a tertiary academic referral center including all subjects that underwent linear accelerator-based stereotactic radiotherapy (SRS) for sporadic VS and completed pre-treatment and post-treatment vestibular testing and Dizziness Handicap Inventory (DHI) questionnaires. Associations between objective vestibular test results, patient-reported DHI scores and radiation dose parameters were investigated. RESULTS: Ten patients met inclusion criteria. Tumor control was achieved in all individuals. There were no statistically significant associations or identifiable trends between radiation dose and change in vestibular function or DHI scores. Notably, the four ears receiving the highest vestibular dose had minimal changes in vestibular function tests and DHI scores. CONCLUSIONS: To the best of our knowledge, no previous reports have described the association between radiation dose to the vestibule and post-treatment changes in vestibular function and patient reported DHI. Based on these preliminary data, radiation dose to the vestibule does not reliably predict change in objective or subjective vestibular outcome measures.

Evaluation of the dynamic conformal arc therapy in comparison to intensity-modulated radiation therapy in prostate, brain, head-and-neck and spine tumors.

To evaluate dynamic conformal arc therapy (DAT) dose distribution and clinical applicability in comparison to intensity modulated radiotherapy (IMRT) in different types of tumors and locations, twelve patients with prostate cancer with no node involvement and three patients with single tumors in the pituitary, in the neck and in the thoracic spinal region treated with IMRT, were retrospectively planned with DAT using Eclipse (V8.1). The prostate cases were also planned with three-dimensional conformal radiation therapy (3DCRT). Dose distributions were evaluated through comparisons of dose-volumetric histograms and in-house IMRT protocol constraints, as well as validated via ion chamber array measurements. DAT plans for prostate showed a statistically comparable achievement of tumor conformity and dose sparing for bladder and rectum when compared to IMRT. Dose on femoral heads were similar to those achieved using 3DCRT. DAT could be planned with similar results to those obtained in IMRT for the dose constraints of the defined structures by using a 360° arc for the brain lesion and several arcs including noncoplanar ones for the head-and-neck and spinal tumors. Experimental validation of the calculated dose distributions via gamma analysis of composite distributions for DAT provided that more than 95% of the pixels satisfy the criteria 3 mm-3%, which was similar to that of IMRT. The average number of monitor units was approximately five times lower than IMRT. In conclusion, DAT is capable of providing conformal dose distributions to the targets accomplishing many of the IMRT dose constraints simultaneously. Experimental dose-validation accuracy, ease of planning and reduced treatment times make DAT both acceptable and attractive for clinical use.

Hypothyroidism as a consequence of intensity-modulated radiotherapy with concurrent taxane-based chemotherapy for locally advanced head-and-neck cancer.

PURPOSE: To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for developing hypothyroidism. METHODS AND MATERIALS: Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose-volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroid was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m(2)) and carboplatin area under the curve-1 were given concurrently with IMRT. RESULTS: Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005). CONCLUSIONS: If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended.