Planning and delivery of intensity modulated bolus electron conformal therapy.

PURPOSE: Bolus electron conformal therapy (BECT) is a clinically useful, well-documented, and available technology. The addition of intensity modulation (IM) to BECT reduces volumes of high dose and dose spread in the planning target volume (PTV). This paper demonstrates new techniques for a process that should be suitable for planning and delivering IM-BECT using passive radiotherapy intensity modulation for electrons (PRIME) devices. METHODS: The IM-BECT planning and delivery process is an addition to the BECT process that includes intensity modulator design, fabrication, and quality assurance. The intensity modulator (PRIME device) is a hexagonal matrix of small island blocks (tungsten pins of varying diameter) placed inside the patient beam-defining collimator (cutout). Its design process determines a desirable intensity-modulated electron beam during the planning process, then determines the island block configuration to deliver that intensity distribution (segmentation). The intensity modulator is fabricated and quality assurance performed at the factory (.decimal, LLC, Sanford, FL). Clinical quality assurance consists of measuring a fluence distribution in a plane perpendicular to the beam in a water or water-equivalent phantom. This IM-BECT process is described and demonstrated for two sites, postmastectomy chest wall and temple. Dose plans, intensity distributions, fabricated intensity modulators, and quality assurance results are presented. RESULTS: IM-BECT plans showed improved D90-10 over BECT plans, 6.4% versus 7.3% and 8.4% versus 11.0% for the postmastectomy chest wall and temple, respectively. Their intensity modulators utilized 61 (single diameter) and 246 (five diameters) tungsten pins, respectively. Dose comparisons for clinical quality assurance showed that for doses greater than 10%, measured agreed with calculated dose within 3% or 0.3 cm distance-to-agreement (DTA) for 99.9% and 100% of points, respectively. CONCLUSION: These results demonstrated the feasibility of translating IM-BECT to the clinic using the techniques presented for treatment planning, intensity modulator design and fabrication, and quality assurance processes.

Filmless quality assurance of a Leksell Gamma Knife® Icon™.

PURPOSE: The annual quality assurance (QA) of Leksell Gamma Knife® (LGK) systems are typically performed using films. Film is a good candidate for small field dosimetry due to its high spatial resolution and availability. However, there are multiple challenges with using film; film does not provide real-time measurement and requires batch-specific calibration. Our findings show that active detector-based QA can simplify the procedure and save time without loss of accuracy. METHODS: Annual QA tests for a LGK Icon™ system were performed using both film-based and filmless techniques. Output calibration, relative output factors (ROF), radiation profiles, sector uniformity/source counting, and verification of the unit center point (UCP) and radiation focal point (RFP) coincidence tests were performed. Radiochromic films, two ionization chambers, and a synthetic diamond detector were used for the measurements. Results were compared and verified with the treatment planning system (TPS). RESULTS: The measured dose rate of the LGK Icon was within 0.4% of the TPS value set at the time of commissioning using an ionization chamber. ROF for the 8 and 4-mm collimators were found to be 0.3% and 1.8% different from TPS values using the MicroDiamond detector and 2.6% and 1.9% different for film, respectively. Excellent agreement was found between TPS and measured dose profiles using the MicroDiamond detector which was within 1%/1 mm vs 2%/1 mm for film. Sector uniformity was found to be within 1% for all eight sectors measured using an ionization chamber. Verification of UCP and RFP coincidence using the MicroDiamond detector and pinprick film test was within 0.3 mm at isocenter for both. CONCLUSION: The annual QA of a LGK Icon was successfully performed by employing filmless techniques. Comparable results were obtained using radiochromic films. Utilizing active detectors instead of films simplifies the QA process and saves time without loss of accuracy.

Evaluation of a new secondary dose calculation software for Gamma Knife radiosurgery.

Current available secondary dose calculation software for Gamma Knife radiosurgery falls short in situations where the target is shallow in depth or when the patient is positioned with a gamma angle other than 90°. In this work, we evaluate a new secondary calculation software which utilizes an innovative method to handle nonstandard gamma angles and image thresholding to render the skull for dose calculation. 800 treatment targets previously treated with our GammaKnife Icon system were imported from our treatment planning system (GammaPlan 11.0.3) and a secondary dose calculation was conducted. The agreement between the new calculations and the TPS were recorded and compared to the original secondary dose calculation agreement with the TPS using a Wilcoxon Signed Rank Test. Further comparisons using a Mann-Whitney test were made for targets treated at a 90° gamma angle against those treated with either a 70 or 110 gamma angle for both the new and commercial secondary dose calculation systems. Correlations between dose deviations from the treatment planning system against average target depth were evaluated using a Kendall's Tau correlation test for both programs. The Wilcoxon Signed Rank Test indicated a significant difference in the agreement between the two secondary calculations and the TPS, with a P-value < 0.0001. With respect to patients treated at nonstandard gamma angles, the new software was largely independent of patient setup, while the commercial software showed a significant dependence (P-value < 0.0001). The new secondary dose calculation software showed a moderate correlation with calculation depth, while the commercial software showed a weak correlation (Tau = -.322 and Tau = -.217 respectively). Overall, the new secondary software has better agreement with the TPS than the commercially available secondary calculation software over a range of diverse treatment geometries.

Characterization and validation of an intra-fraction motion management system for masked-based radiosurgery.

PURPOSE: Characterize the intra-fraction motion management (IFMM) system found on the Gamma Knife Icon (GKI), including spatial accuracy, latency, temporal performance, and overall effect on delivered dose. METHODS: A phantom was constructed, consisting of a three-axis translation mount, a remote motorized flipper, and a thermoplastic sphere surrounding a radiation detector. An infrared marker was placed on the translation mount secured to the flipper. The spatial accuracy of the IFMM was measured via the translation mount in all Cartesian planes. The detector was centered at the radiation focal point. A remote signal was used to move the marker out of the IFMM tolerance and pause the beam. A two-channel electrometer was used to record the signals from the detector and the flipper when motion was signaled. These signals determined the latency and temporal performance of the GKI. RESULTS: The spatial accuracy of the IFMM was found to be <0.1 mm. The measured latency was <200 ms. The dose difference with five interruptions was <0.5%. CONCLUSION: This work provides a quantitative characterization of the GKI IFMM system as required by the Nuclear Regulatory Commission. This provides a methodology for GKI users to satisfy these requirements using common laboratory equipment in lieu of a commercial solution.

Script-based implementation of automatic grid placement for lattice stereotactic body radiation therapy.

Background and purpose: Spatially fractionated radiation therapy (SFRT) has demonstrated promising clinical response in treating large tumors with heterogeneous dose distributions. Lattice stereotactic body radiation therapy (SBRT) is an SFRT technique that leverages inverse optimization to precisely localize regions of high and lose dose within disease. The aim of this study was to evaluate an automated heuristic approach to sphere placement in lattice SBRT treatment planning. Materials and methods: A script-based algorithm for sphere placement in lattice SBRT based on rules described by protocol was implemented within a treatment planning system. The script was applied to 22 treated cases and sphere distributions were compared with manually placed spheres in terms of number of spheres, number of protocol violations, and time required to place spheres. All cases were re-planned using script-generated spheres and plan quality was compared with clinical plans. Results: The mean number of spheres placed excluding those that violate rules was greater using the script (13.8) than that obtained by either dosimetrist (10.8 and 12.0, p < 0.001 and p = 0.003) or physicist (12.7, p = 0.061). The mean time required to generate spheres was significantly less using the script (2.5 min) compared to manual placement by dosimetrists (25.0 and 29.9 min) and physicist (19.3 min). Plan quality indices were similar in all cases with no significant differences, and OAR constraints remained met on all plans except two. Conclusion: A script placed spheres for lattice SBRT according to institutional protocol rules. The script-produced placement was superior to that of manually-specified spheres, as characterized by sphere number and rule violations.

Automated target placement for VMAT lattice radiation therapy: enhancing efficiency and consistency.

Objective. An algorithm was developed for automated positioning of lattice points within volumetric modulated arc lattice radiation therapy (VMAT LRT) planning. These points are strategically placed within the gross tumor volume (GTV) to receive high doses, adhering to specific separation rules from adjacent organs at risk (OARs). The study goals included enhancing planning safety, consistency, and efficiency while emulating human performance.Approach. A Monte Carlo-based algorithm was designed to optimize the number and arrangement of lattice points within the GTV while considering placement constraints and objectives. These constraints encompassed minimum spacing between points, distance from OARs, and longitudinal separation along thez-axis. Additionally, the algorithm included an objective to permit, at the user's discretion, solutions with more centrally placed lattice points within the GTV. To validate its effectiveness, the automated approach was compared with manually planned treatments for 24 previous patients. Prior to clinical implementation, a failure mode and effects analysis (FMEA) was conducted to identify potential shortcomings.Main results.The automated program successfully met all placement constraints with an average execution time (over 24 plans) of 0.29 ±0.07 min per lattice point. The average lattice point density (# points per 100 c.c. of GTV) was similar for automated (0.725) compared to manual placement (0.704). The dosimetric differences between the automated and manual plans were minimal, with statistically significant differences in certain metrics like minimum dose (1.9% versus 1.4%), D5% (52.8% versus 49.4%), D95% (7.1% versus 6.2%), and Body-GTV V30% (20.7 c.c. versus 19.7 c.c.).Significance.This study underscores the feasibility of employing a straightforward Monte Carlo-based algorithm to automate the creation of spherical target structures for VMAT LRT planning. The automated method yields similar dose metrics, enhances inter-planner consistency for larger targets, and requires fewer resources and less time compared to manual placement. This approach holds promise for standardizing treatment planning in prospective patient trials and facilitating its adoption across centers seeking to implement VMAT LRT techniques.

Overview and Recommendations for Prospective Multi-institutional Spatially Fractionated Radiation Therapy Clinical Trials.

PURPOSE: The highly heterogeneous dose delivery of spatially fractionated radiation therapy (SFRT) is a profound departure from standard radiation planning and reporting approaches. Early SFRT studies have shown excellent clinical outcomes. However, prospective multi-institutional clinical trials of SFRT are still lacking. This NRG Oncology/American Association of Physicists in Medicine working group consensus aimed to develop recommendations on dosimetric planning, delivery, and SFRT dose reporting to address this current obstacle toward the design of SFRT clinical trials. METHODS AND MATERIALS: Working groups consisting of radiation oncologists, radiobiologists, and medical physicists with expertise in SFRT were formed in NRG Oncology and the American Association of Physicists in Medicine to investigate the needs and barriers in SFRT clinical trials. RESULTS: Upon reviewing the SFRT technologies and methods, this group identified challenges in several areas, including the availability of SFRT, the lack of treatment planning system support for SFRT, the lack of guidance in the physics and dosimetry of SFRT, the approximated radiobiological modeling of SFRT, and the prescription and combination of SFRT with conventional radiation therapy. CONCLUSIONS: Recognizing these challenges, the group further recommended several areas of improvement for the application of SFRT in cancer treatment, including the creation of clinical practice guidance documents, the improvement of treatment planning system support, the generation of treatment planning and dosimetric index reporting templates, and the development of better radiobiological models through preclinical studies and through conducting multi-institution clinical trials.

A Dose Accumulation Assessment of Alignment Errors During Spatially Fractionated Radiation Therapy.

PURPOSE: Spatially fractionated radiation therapy (SFRT) techniques produce high-dose peaks and low-dose valleys within a tumor. Lattice stereotactic body radiation therapy (SBRT) is a form a SFRT delivered across 5 fractions. Because of the high spatial dose gradients associated with SFRT, it is critical for fractionated SFRT patients to be aligned correctly for treatment. Here we investigate the dosimetric effect of daily alignment uncertainty through a dose accumulation study. METHODS AND MATERIALS: Dose accumulation was retrospectively performed for 10 patients enrolled on a phase 1 trial. Lattice stereotactic body radiation therapy was completed in 5 fractions with 20 Gy prescribed to the entire tumor and a simultaneous integrated boost of 66.7 Gy prescribed to a set of regularly spaced high-dose spheres. Daily alignment error was quantified through manually selected landmarks in both the planning computed tomography scan and daily cone beam computed tomography. The dosimetric effect of alignment errors was quantified by translating the isocenter in the treatment planning system by the daily average alignment error. Large errors were simulated by translating isocenter 5 and 10 mm for 1 and 2 fractions, independently assessing errors in the superior-inferior and axial directions. The reduction of dose gradients was quantified using the dose ratio (DR) of the mean dose in the high-dose and low-dose spheres. RESULTS: The average alignment error was 1.8 mm across the patient population resulting in minor smoothing of the high- and low-dose distributions in the dose accumulation. Quantitatively, the DR decreased from 3.42 to 3.32 (P = .093) in the dose accumulation study. The simulated worst case was an inferior-superior shift of 10 mm for 2 fractions where the average DR decreased to 2.72 (P = .0001). CONCLUSIONS: The dose accumulation study revealed on average DR only decreased from 3.42 to 3.32. However, setup errors >5 mm resulted in larger dosimetric degradation, reflecting a larger effect for individual high-dose spheres within regions exhibiting larger displacements.

First treatments for Lattice stereotactic body radiation therapy using magnetic resonance image guided radiation therapy.

Two abdominal patients were treated with Lattice stereotactic body radiation therapy (SBRT) using magnetic resonance guided radiation therapy (MRgRT). This is one of the first reported treatments of Lattice SBRT with the use of MRgRT. A description of the treatment approach and planning considerations were incorporated into this report. MRgRT Lattice SBRT delivered similar planning quality metrics to established dosimetric parameters for Lattice SBRT. Increased signal intensity were seen in the MRI treatments for one of the patients during the course of treatment.

Clinical aspects of spatially fractionated radiation therapy treatments.

PURPOSE: To provide clinical guidance for centers wishing to implement photon spatially fractionated radiation therapy (SFRT) treatments using either a brass grid or volumetric modulated arc therapy (VMAT) lattice approach. METHODS: We describe in detail processes which have been developed over the course of a 3-year period during which our institution treated over 240 SFRT cases. The importance of patient selection, along with aspects of simulation, treatment planning, quality assurance, and treatment delivery are discussed. Illustrative examples involving clinical cases are shown, and we discuss safety implications relevant to the heterogeneous dose distributions. RESULTS: SFRT can be an effective modality for tumors which are otherwise challenging to manage with conventional radiation therapy techniques or for patients who have limited treatment options. However, SFRT has several aspects which differ drastically from conventional radiation therapy treatments. Therefore, the successful implementation of an SFRT treatment program requires the multidisciplinary expertise and collaboration of physicians, physicists, dosimetrists, and radiation therapists. CONCLUSIONS: We have described methods for patient selection, simulation, treatment planning, quality assurance and delivery of clinical SFRT treatments which were built upon our experience treating a large patient population with both a brass grid and VMAT lattice approach. Preclinical research and patient trials aimed at understanding the mechanism of action are needed to elucidate which patients may benefit most from SFRT, and ultimately expand its use.

LITE SABR M1: Planning design and dosimetric endpoints for a phase I trial of lattice SBRT.

PURPOSE: Lattice stereotactic body radiation therapy (SBRT) is a form of spatially fractionated radiation therapy (SFRT) using SBRT methods. This study reports clinical dosimetric endpoints achieved for Lattice SBRT plans delivering 20 Gy in 5 fractions to the periphery of a tumor with a simultaneous integrated boost (SIB) of 66.7 Gy, as part of a prospective Phase I clinical trial (NCT04133415). Additionally, it updates previously reported planning and delivery techniques based on extended experience with a broader patient population. METHODS: Patients were enrolled on a single-arm phase I trial conducted between November 2019 and August 2020. Eligibility was restricted to tumors >4.5 cm in the largest dimension. Characteristic SFRT dose gradients were achieved using a lattice of 1.5 cm diameter spheres spaced within the GTV in a regular pattern, with peak-to-valley dose varying from 66.7 Gy to 20 Gy within 1.5 cm. Organ-at-risk (OAR) sparing followed AAPM TG101 recommendations for 5-fraction SBRT. RESULTS: Twenty patients (22 plans) were enrolled on study, with one additional plan treated off study. All OAR and target coverage planning objectives were achieved, with the exception of a single small bronchus. Conformity of the 20 Gy isodose line significantly improved over the course of the study. The majority (85.2%) of treatment fractions were delivered in a 30 minutes timeslot, with 4 (3.5%) exceeding a total treatment time of 40 minutes. CONCLUSION: Lattice SBRT planning techniques produce consistent and efficient treatment plans. Refined techniques described here further improve the quality of the planning technique.

Techno-Economic Feasibility Analysis of a Fully Mobile Radiation Oncology System Using Monte Carlo Simulation.

PURPOSE: Disparities in radiation oncology (RO) can be attributed to geographic location, socioeconomic status, race, sex, and other societal factors. One potential solution is to implement a fully mobile (FM) RO system to bring radiotherapy to rural areas and reduce barriers to access. We use Monte Carlo simulation to quantify techno-economic feasibility with uncertainty, using two rural Missouri scenarios. METHODS: Recently, a semimobile RO system has been developed by building an o-ring linear accelerator (linac) into a mobile coach that is used for temporary care, months at a time. Transitioning to a more FM-RO system, which changes location within a given day, presents technical challenges including logistics and quality assurance. This simulation includes cancer census in both northern and southeastern Missouri, multiple treatment locations within a given day, and associated expenditures and revenues. A subset of patients with lung, breast, and rectal diseases, treated with five fractions, was simulated in the FM-RO system. RESULTS: The FM-RO can perform all necessary quality assurance tests as suggested in national medical physics guidelines within 1.5 hours, thus demonstrating technological feasibility. In northern and southeastern Missouri, five-fraction simulations' net incomes were, in US dollars (USD), $1.55 ± 0.17 million (approximately 74 patients/year) and $3.65 USD ± 0.25 million (approximately 98 patients/year), respectively. The number of patients seen had the highest correlation with net income as well as the ability to break-even within the simulation. The model does not account for disruptions in care or other commonly used treatment paradigms, which may lead to differences in estimated economic return. Overall, the mobile system achieved a net benefit, even for the most negative simulation scenarios. CONCLUSION: Our simulations suggest technologic success and economic viability for a FM-RO system within rural Missouri and present an interesting solution to address other geographic disparities in access to radiotherapy.

LITE SABR M1: A phase I trial of Lattice stereotactic body radiotherapy for large tumors.

PURPOSE: Stereotactic body radiotherapy (SBRT) is an attractive treatment option for patients with metastatic and/or unresectable tumors, however its use is limited to smaller tumors. Lattice is a form of spatially fractionated radiotherapy that may allow safe delivery of ablative doses to bulky tumors. We previously described Lattice SBRT, which delivers 20 Gy in 5 fractions with a simultaneous integrated boost to 66.7 Gy in a defined geometric arrangement (Lattice boost). The goal of this study was to prospectively evaluate the acute toxicity and quality of life (QoL) of patients with large tumors (>5 cm) treated with Lattice SBRT. METHODS: This was a single-arm phase I trial conducted between October 2019 and August 2020. Patients with tumors > 4.5 cm were eligible. Lattice SBRT was delivered every other day. The primary outcome was the rate of 90-day treatment-associated (probably or definitely attributable) grade 3 + acute toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Other outcomes included changes in patient reported toxicity and QoL inventories, GTV, and peripheral blood cytokines. RESULTS: Twenty patients (22 tumors) were enrolled. Median GTV was 579.2 cc (range: 54.2-3713.5 cc) in volume and 11.1 cm (range: 5.6-21.4 cm) in greatest axial diameter. Fifty percent of tumors were in the thorax, 45% abdomen/pelvis, and 5% extremity. There was no likely treatment-associated grade 3 + toxicity in the 90-day period (acute and sub-acute). There was one case of grade 4 toxicity possibly associated with Lattice SBRT. CONCLUSIONS: This phase I study met its primary endpoint of physician reported short-term safety. An ongoing phase II clinical trial of Lattice SBRT will evaluate late safety and efficacy of this novel technique.

A method for predictive modeling of tumor regression for lung adaptive radiotherapy.

PURPOSE: The purpose of this work is to create a decision support methodology to predict when patients undergoing radiotherapy treatment for locally advanced lung cancer would potentially benefit from adaptive radiotherapy. The proposed methodology seeks to eliminate the manual subjective review by developing an automated statistical learning model to predict when tumor regression would trigger implementation of adaptive radiotherapy based on quantified anatomic changes observed in individual patients on-treatment cone beam computed tomographies (CTs). This proposed process seeks to improve the efficacy and efficiency of both the existing manual and automated adaptive review processes for locally advanced stage III lung cancer. METHODS: A predictive algorithm was developed as a decision support tool to determine the potential utility of mid-treatment adaptive radiotherapy based on anatomic changes observed on 1158 daily CBCT images across 43 patients. The anatomic changes on each axial slice within specified regions-of-interest were quantified into a single value utilizing imaging similarity criteria comparing the daily CBCT to the initial simulation CT. The range of the quantified metrics for each fraction across all axial slices are reduced to specified quantiles, which are used as the predictive input to train a logistic regression algorithm. A "ground-truth" of the need for adaptive radiotherapy based on tumor regression was evaluated systematically on each of the daily CBCTs and used as the classifier in the logistic regression algorithm. Accuracy of the predictive model was assessed utilizing both a tenfold cross validation and an independent validation dataset, with the sensitivity, specificity, and fractional accuracy compared to the ground-truth. RESULTS: The sensitivity and specificity for the individual daily fractions ranged from 87.9%-94.3% and 91.9%-98.6% for a probability threshold of 0.2-0.5, respectively. The corresponding average treatment fraction difference between the model predictions and assessed ART "ground-truth" ranged from -2.25 to -0.07 fractions, with the model predictions consistently predicting the potential need for ART earlier in the treatment course. By initially utilizing a lower probability threshold, the higher sensitivity minimizes the chance of false negative by alerting the clinician to review a higher number of questionable cases. CONCLUSIONS: The proposed methodology accurately predicted the first fraction at which individual patients may benefit from ART based on quantified anatomic changes observed in the on-treatment volumetric imaging. The generalizability of the proposed method has potential to expand to additional modes of adaptive radiotherapy for lung cancer patients with observed underlying anatomic changes.

Robustness of deep learning segmentation of cardiac substructures in noncontrast computed tomography for breast cancer radiotherapy.

PURPOSE: To develop and evaluate deep learning-based autosegmentation of cardiac substructures from noncontrast planning computed tomography (CT) images in patients undergoing breast cancer radiotherapy and to investigate the algorithm sensitivity to out-of-distribution data such as CT image artifacts. METHODS: Nine substructures including aortic valve (AV), left anterior descending (LAD), tricuspid valve (TV), mitral valve (MV), pulmonic valve (PV), right atrium (RA), right ventricle (RV), left atrium (LA), and left ventricle (LV) were manually delineated by a radiation oncologist on noncontrast CT images of 129 patients with breast cancer; among them 90 were considered in-distribution data, also named as "clean" data. The image/label pairs of 60 subjects were used to train a 3D deep neural network while the remaining 30 were used for testing. The rest of the 39 patients were considered out-of-distribution ("outlier") data, which were used to test robustness. Random rigid transformations were used to augment the dataset during training. We investigated multiple loss functions, including Dice similarity coefficient (DSC), cross-entropy (CE), Euclidean loss as well as the variation and combinations of these, data augmentation, and network size on overall performance and sensitivity to image artifacts due to infrequent events such as the presence of implanted devices. The predicted label maps were compared to the ground-truth labels via DSC and mean and 90th percentile symmetric surface distance (90th-SSD). RESULTS: When modified Dice combined with cross-entropy (MD-CE) was used as the loss function, the algorithm achieved a mean DSC = 0.79 ± 0.07 for chambers and  0.39 ± 0.10 for smaller substructures (valves and LAD). The mean and 90th-SSD were 2.7 ± 1.4 and 6.5 ± 2.8 mm for chambers and 4.1 ± 1.7 and 8.6 ± 3.2 mm for smaller substructures. Models with MD-CE, Dice-CE, MD, and weighted CE loss had highest performance, and were statistically similar. Data augmentation did not affect model performances on both clean and outlier data and model robustness was susceptible to network size. For a certain type of outlier data, robustness can be improved via incorporating them into the training process. The execution time for segmenting each patient was on an average 2.1 s. CONCLUSIONS: A deep neural network provides a fast and accurate segmentation of large cardiac substructures in noncontrast CT images. Model robustness of two types of clinically common outlier data were investigated and potential approaches to improve them were explored. Evaluation of clinical acceptability and integration into clinical workflow are pending.

Spatially fractionated stereotactic body radiation therapy (Lattice) for large tumors.

PURPOSE: Stereotactic body radiation therapy (SBRT) has demonstrated clinical benefits for patients with metastatic and/or unresectable cancer. Technical considerations of treatment delivery and nearby organs at risk can limit the use of SBRT in large tumors or those in unfavorable locations. Spatially fractionated radiation therapy (SFRT) may address this limitation because this technique can deliver high-dose radiation to discrete subvolume vertices inside a tumor target while restricting the remainder of the target to a safer lower dose. Indeed, SFRT, such as GRID, has been used to treat large tumors with reported dramatic tumor response and minimal side effects. Lattice is a modern approach to SFRT delivered with arc-based therapy, which may allow for safe, high-quality SBRT for large and/or deep tumors. METHODS AND MATERIALS: Herein, we report the results of a dosimetry and quality assurance feasibility study of Lattice SBRT in 11 patients with 12 tumor targets, each ≥10 cm in an axial dimension. Prior computed tomography simulation scans were used to generate volumetric modulated arc therapy Lattice SBRT plans that were then delivered on clinically available Linacs. Quality assurance testing included external portal imaging device and ion chamber analyses. RESULTS: All generated plans met the standard SBRT dose constraints, such as those from the American Association of Physicists in Medicine Task Group 101. Additionally, we provide a step-by-step approach to generate and deliver Lattice SBRT plans using commercially available treatment technology. CONCLUSIONS: Lattice SBRT is currently being tested in a prospective trial for patients with metastatic cancer who need palliation of large tumors (NCT04553471, NCT04133415).

Internal dose escalation associated with increased local control for melanoma brain metastases treated with stereotactic radiosurgery.

OBJECTIVE: The internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non-small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM. METHODS: The records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC. RESULTS: Two hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31-86 years). The median follow-up was 7.6 months (range 0.5-81.6 months), and the median survival was 9.3 months (range 1.3-81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was ≥ and < 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 ≥ and < 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 ≥ and < 25%, respectively. Lesions > 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 ≥ and < 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30. CONCLUSIONS: For a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 ≥ 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation.

Anatomical Adaptation-Early Clinical Evidence of Benefit and Future Needs in Lung Cancer.

Definitive treatment of locally advanced non-small-cell lung cancer with radiation is challenging. During the course of treatment, anatomical changes such as tumor regression, tumor displacement/deformation, pleural effusion, and/or atelectasis can result in a deviation of the administered radiation dose from the intended prescribed treatment and thereby worsen local control and toxicity. Adaptive radiotherapy can help correct for these changes and can be generally categorized into 3 philosophical paradigms: (1) maintenance of prescribed dose to the initially defined target volume; (2) dose reduction to healthy organs while maintaining initial prescribed dose to a regressing tumor volume; or (3) dose escalation to a regressing tumor volume with isotoxicity to healthy organs. Numerous single institution studies have investigated these methods, and results from large prospective clinical trials will hopefully provide consensus on the method, utility, and efficacy of implementing adaptive radiation therapy (ART) in a clinical setting. Additional development into standardization and automation of the ART workflow, specifically in identifying when ART is warranted and in reducing the manual clinical effort needed to produce an adaptive plan, will be paramount to making ART feasible for the broader radiation therapy community.