Technical feasibility of novel immunostimulatory low-dose radiation for polymetastatic disease with CBCT-based online adaptive and conventional approaches.

PURPOSE: A workflow/planning strategy delivering low-dose radiation therapy (LDRT) (1 Gy) to all polymetastatic diseases using conventional planning/delivery (Raystation/Halcyon = "conventional") and the AI-based Ethos online adaptive RT (oART) platform is developed/evaluated. METHODS: Using retrospective data for ten polymetastatic non-small cell lung cancer patients (5-52 lesions each) with PET/CTs, gross tumor volumes (GTVs) were delineated using PET standardized-uptake-value (SUV) thresholding. A 1 cm uniform expansion of GTVs to account for setup/contour uncertainty and organ motion-generated planning target volumes (PTVs). Dose optimization/calculation used the diagnostic CT from PET/CT. Dosimetric objectives were: Dmin,0.03cc ≥ 95% (acceptable variation (Δ) ≥ 90%), V100% ≥ 95% (Δ ≥ 90%), and D0.03cc ≤ 120% (Δ ≤ 125%). Additionally, online adaptation was simulated. When available, subsequent diagnostic CT was used to represent on-treatment CBCT. Otherwise, the CT from PET/CT used for initial planning was deformed to simulate clinically representative changes. RESULTS: All initial plans generated, both for Raystation and Ethos, achieved clinical goals within acceptable variation. For all patients, Dmin,0.03cc ≥ 95%, V100% ≥ 95%, and D0.03cc ≤ 120% goals were achieved for 84.8%/99.5%, 97.7%/98.7%, 97.4%/92.3%, in conventional/Ethos plans, respectively. The ratio of 50% isodose volume to PTV volume (R50%), maximum dose at 2 cm from PTV (D2cm), and the ratio of the 100% isodose volume to PTV volume (conformity index) in Raystation/Ethos plans were 7.9/5.9; 102.3%/88.44%; and 0.99/1.01, respectively. In Ethos, online adapted plans maintained PTV coverage whereas scheduled plans often resulted in geographic misses due to changes in tumor size, patient position, and body habitus. The average total duration of the oART workflow was 26:15 (min:sec) ranging from 6:43 to 57:30. The duration of each oART workflow step as a function of a number of targets showed a low correlation coefficient for influencer generation and editing (R2 = 0.04 and 0.02, respectively) and high correlation coefficient for target generation, target editing and plan generation (R2 = 0.68, 0.63 and 0.69, respectively). CONCLUSIONS: This study demonstrates feasibility of conventional planning/treatment with Raystation/Halcyon and highlights efficiency gains when utilizing semi-automated planning/online-adaptive treatment with Ethos for immunostimulatory LDRT conformally delivered to all sites of polymetastatic disease.

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.

Feasibility and Toxicity of Full-Body Volumetric Modulated Arc Therapy Technique for High-Dose Total Body Irradiation.

Introduction: High-dose total body irradiation (TBI) is often part of myeloablative conditioning in acute leukemia. Modern volumetric modulated arc therapy (VMAT)-based plans employ arcs to the inferior-most portion of the body that can be simulated in a head-first position and use 2D planning for the inferior body which can result in heterogeneous doses. Here, we describe our institution's unique protocol for delivering high-dose TBI entirely with VMAT and retrospectively compare dosimetric outcomes with helical tomotherapy (HT) plans. Additionally, we describe our method of oropharyngeal mucosal sparing that was implemented after fatal mucositis occurred in two patients. Methods: Thirty-one patients were simulated and treated in head-first (HFS) and feet-first (FFS) orientations. Patients were treated with VMAT (n = 26) or HT (n = 5). In VMAT plans, to synchronize doses between the orientations, images were deformably registered and the HFS dose was transferred to the FFS plan and used as a background dose when optimizing plans. Six to eight isocenters with two arcs per isocenter were generated. HT was delivered with an established technique. Patients were treated to 13.2 Gy over eight twice daily fractions. Dosimetric outcomes and toxicities were retrospectively compared. Results: Prescription dose and organ at risk (OAR) constraints were met for all patients. Lower lung doses were achieved with VMAT relative to HT plans (7.4 vs 7.7 Gy, P = .009). Statistically significant improvement in mucositis was not achieved after adopting a mucosal-sparing technique, however lower doses to the oropharyngeal mucosal were achieved (6.9 vs 14.1 Gy, P = .009), and no further mucositis-related deaths occurred. Conclusions: This full-body VMAT method of TBI achieves dose goals, eliminates risk of heterogenous doses within the femur, and demonstrates that selective OAR sparing with the purpose of reducing TBI-related morbidity and mortality is possible at any institution with a VMAT-capable linear accelerator.

Revisiting the Concept of Recurrence of Primary Central Nervous System Lymphomas After Complete Response to Methotrexate-Based Therapy: Periventricular Reseeding as the Predominant Mechanism of Recurrence.

Purpose: Understanding patterns of relapse for primary central nervous system lymphoma (PCNSL) may inform mechanisms of recurrence and optimal consolidation strategies. In this study, we report patterns of relapse among patients with PCNSL who achieved a complete response to high-dose methotrexate (HD-MTX)-based chemotherapy with or without consolidation radiation therapy (RT). Methods and Materials: We conducted an institutional retrospective analysis of patients with PCNSL who received HD-MTX-based chemotherapy between November 2001 and May 2019. Relapses were characterized as in-field (within original T1 contrasted lesion), marginal (within T2 fluid-attenuated inversion recovery but not T1), local (in-field or marginal), distant brain (no overlap), or distant (distant brain, cerebrospinal fluid, vitreous or extra-axial) and further characterized with respect to periventricular location (≤10 mm of ventricles). Results: Seventy-eight patients with PCNSL met inclusion criteria, of whom 29 (37%) underwent consolidation RT. Median progression-free survival and overall survival were 57.0 and 66.7 months, respectively. After a median follow-up of 38.9 months, a total of 32 patients (41%) experienced recurrence. Most patients (21 [65.6%]) had a periventricular failure. Surprisingly, local recurrences (n = 11) were exclusively observed within periventricular lesions, whereas distant recurrences (n = 21) were seen in both periventricular and nonperiventricular locations (P = .009). The median time to progression was shorter for locally recurrent lesions compared with distant recurrences (13.8 vs 26.1 months; P = .03). Conclusions: After complete response to HD-MTX, few failures occurred within initial T1 contrast-enhancing lesions and many of these may have been alternatively classified as periventricular failures. These observations argue against the use of purely focal RT consolidation for patients who achieve a complete response after HD-MTX-based chemotherapy and suggest that periventricular reseeding may have a central role in PCNSL recurrence.

Cluster model incorporating heterogeneous dose distribution of partial parotid irradiation for radiotherapy induced xerostomia prediction with machine learning methods.

PURPOSE: A cluster model incorporating heterogeneous dose distribution within the parotid gland was developed and validated retrospectively for radiotherapy (RT) induced xerostomia prediction with machine learning (ML) techniques. METHODS: Sixty clusters were obtained at 1 Gy step size with threshold doses ranging from 1 to 60 Gy, for each of the enrolled 155 patients with HNC from three institutions. Feature clusters were selected with the neighborhood component analysis (NCA) and subsequently fed into four supervised ML models for xerostomia prediction comparison: support vector machines (SVM), k-nearest neighbor (kNN), naïve Bayes (NB), and random forest (RF). The predictive performance of each model was evaluated using cross validation resampling with the area-under-the-curves (AUC) of the receiver-operating-characteristic (ROC). The xerostomia predicting capacity using testing data was assessed with accuracy, sensitivity, and specificity for these models and three cluster connectivity choices. Mean dose based logistic regression served as the benchmark for evaluation. RESULTS: Feature clusters identified by NCA fell in three threshold dose ranges: 5-15Gy, 25-35Gy, and 45-50Gy. Mean dose predictive power was 15% lower than that of the cluster model using the logistic regression classifier. Model validation demonstrated that kNN model outperformed slightly other three models but no substantial difference was observed. Applying the fine-tuned models to testing data yielded that the mean accuracy from SVM, kNN and NB models were between 0.68 and 0.7 while that of RF was ∼0.6. SVM model yielded the best sensitivity (0.76) and kNN model delivered consistent sensitivity and specificity. This is consistent with cross validation. Clusters calculated with three connectivity choices exhibited minimally different predictions. CONCLUSION: Compared to mean dose, the proposed cluster model has shown its improvement as the xerostomia predictor. When combining with ML techniques, it could provide a clinically useful tool for xerostomia prediction and facilitate decision making during radiotherapy planning for patients with HNC.

Feasibility Study of 3D-VMAT-Based GRID Therapy.

Background: Spatially fractionated radiotherapy (GRID) could effectively de-bulk tumor volumes for shallow and deep-seated locally advanced tumors. A new treatment planning method using the three-dimensional-volumetric modulated arc therapy (VMAT) technique combined with a novel, software-generated, virtual GRID block (VGB) was developed which allows better conformity plans (VMAT-GRID) and maintain the GRID dosimetric characteristics. The dosimetric metrics calculated via the valley/peak ratio (Dmin/Dmax), D90/D10, gross tumor volume (GTV) mean dose (Dmean), GTV equivalent uniform dose (EUD), and normal tissue maximum dose. Methods: Twenty-five patients with tumor volumes ranging between 71.6 cc and 4683 cc at various tumor sites were retrospectively studied. The prescription was 20 Gy to the maximum point of GTV in a single fraction, and the VMAT-GRID plan was generated using 6 MV/10 MV flattening-filter-free beams. Results: The optimized VGB was designed with the median center-to-center distance of 27 mm, and 9 mm for the median diameter of the opening area in this study. These 2 values can be used to design any optimized VGB, the final VGB may be modified to generate a patient-specific VGB. The median GTV mean dose was 918 (877- 938) cGy, and the median GTV EUD dose was 818 (597-916) cGy. In terms of dose inhomogeneity, the median valley-to-peak dose ratio was 0.07 (0.02-0.26); and the median ratio of D90/D10 was 0.70 (0.38-0.94). For the organ-at-risk doses, there was a rapid dose drop-off in the normal tissue area immediately adjacent to the target, and the maximum global doses were all located inside the GTV. Conclusion: Our results indicated that the VMAT-GRID planning approach could successfully deliver dose with acceptable GRID dose metric while sparing the normal tissue especially in the region near the target due to the rapid dose drop-off and restricting maximum dose inside the target.

An International Consensus on the Design of Prospective Clinical-Translational Trials in Spatially Fractionated Radiation Therapy.

PURPOSE: Spatially fractionated radiation therapy (SFRT), which delivers highly nonuniform dose distributions instead of conventionally practiced homogeneous tumor dose, has shown high rates of clinical response with minimal toxicities in large-volume primary or metastatic malignancies. However, prospective multi-institutional clinical trials in SFRT are lacking, and SFRT techniques and dose parameters remain variable. Agreement on dose prescription, technical administration, and clinical and translational design parameters for SFRT trials is essential to enable broad participation and successful accrual to rigorously test the SFRT approach. We aimed to develop a consensus for the design of multi-institutional clinical trials in SFRT, tailored to specific primary tumor sites, to help facilitate development and enhance the feasibility of such trials. METHODS AND MATERIALS: Primary tumor sites with sufficient pilot experience in SFRT were identified, and fundamental trial design questions were determined. For each tumor site, a comprehensive consensus effort was established through disease-specific expert panels. Clinical trial design criteria included eligibility, SFRT technology and technique, dose and fractionation, target- and normal-tissue dose parameters, systemic therapies, clinical trial endpoints, and translational science considerations. Iterative appropriateness rank voting, expert panel consensus reviews and discussions, and public comment posting were used for consensus development. RESULTS: Clinical trial criteria were developed for head and neck cancer and soft-tissue sarcoma. Final consensus among the 22 trial design categories each (a total of 163 criteria) was high to moderate overall. Uniform patient cohorts of advanced bulky disease, standardization of SFRT technologies and dosimetry and physics parameters, and collection of translational correlates were considered essential to trial design. Final guideline recommendations and the degree of agreement are presented and discussed. CONCLUSIONS: This consensus provides design guidelines for the development of prospective multi-institutional clinical trials testing SFRT in advanced head and neck cancer and soft-tissue sarcoma through in-advance harmonization of the fundamental clinical trial design among SFRT experts, potential investigators, and the SFRT community.

A dosimetric comparative analysis of Brainlab elements and Eclipse RapidArc for spine SBRT treatment planning.

Purpose. This is a dosimetric study comparing stereotactic body radiotherapy (SBRT) plans of spine tumors using Brainlab Elements Spine planning module against Eclipse RapidArc plans. Dose conformity, dose gradient, dose fall-off, and patient-specific quality assurance (QA) metrics were evaluated. Methods:Twenty patients were immobilized in supine position using half Vac-Lok. A prescription dose of 16 Gy in a single fraction was planned for Varian TrueBeam. Conformal arc plans were generated with Pencil beam (PB), MonteCarlo (MC) in Elements, and RapidArc with Acuros XB algorithm in Eclipse using identical treatment geometry.Results. Eclipse, Elements PB, and Elements MC generated dosimetrically conformal plans having Inverse Paddick Conformity Index (IPCI) <1.3. All plans satisfied the dose constraints to target and OARs. Elements PB had a sharper gradient than Elements MC with average GI of 3.67(95% CI: 3.52-3.82) and 4.06 (95% CI: 3.93-4.20) respectively. Eclipse plans were more homogeneous with mean HI = 1.22 (95% CI: 1.20-1.23) that is lower than others. Average maximum clinical target volume (CTV) doses were higher in Elements MC with 22.31 Gy (95% CI: 21.87-22.74), while PB plans have 21.15 Gy (95% CI: 20.36-21.96), respectively. Elements MC and PB plans had lower average dose to 0.35 c.c. of spinal cord (D0.35cc) of 7.60 Gy (95% CI: 7.18-8.02) and 8.42 Gy (95% CI: 7.83-9.01). All plans had >95% points passing the gamma QA criteria at 3%/2 mm.Conclusion. All treatment plans achieved clinically acceptable target coverage >95% and meet spinal cord dose limits. Smart optimization in Brainlab Elements spine module produced dosimetrically superior plans by better spinal cord sparing.

Triggered kV Imaging During Spine SBRT for Intrafraction Motion Management.

Purpose: To monitor intrafraction motion during spine stereotactic body radiotherapy(SBRT) treatment delivery with readily available technology, we implemented triggered kV imaging using the on-board imager(OBI) of a modern medical linear accelerator with an advanced imaging package. Methods: Triggered kV imaging for intrafraction motion management was tested with an anthropomorphic phantom and simulated spine SBRT treatments to the thoracic and lumbar spine. The vertebral bodies and spinous processes were contoured as the image guided radiotherapy(IGRT) structures specific to this technique. Upon each triggered kV image acquisition, 2D projections of the IGRT structures were automatically calculated and updated at arbitrary angles for display on the kV images. Various shifts/rotations were introduced in x, y, z, pitch, and yaw. Gantry-angle-based triggering was set to acquire kV images every 45°. A group of physicists/physicians(n = 10) participated in a survey to evaluate clinical efficiency and accuracy of clinical decisions on images containing various phantom shifts. This method was implemented clinically for treatment of 42 patients(94 fractions) with 15 second time-based triggering. Result: Phantom images revealed that IGRT structure accuracy and therefore utility of projected contours during triggered imaging improved with smaller CT slice thickness. Contouring vertebra superior and inferior to the treatment site was necessary to detect clinically relevant phantom rotation. From the survey, detectability was proportional to the shift size in all shift directions and inversely related to the CT slice thickness. Clinical implementation helped evaluate robustness of patient immobilization. Based on visual inspection of projected IGRT contours on planar kV images, appreciable intrafraction motion was detected in eleven fractions(11.7%). Discussion: Feasibility of triggered imaging for spine SBRT intrafraction motion management has been demonstrated in phantom experiments and implementation for patient treatments. This technique allows efficient, non-invasive monitoring of patient position using the OBI and patient anatomy as a direct visual guide.

Practice Patterns of Pediatric Total Body Irradiation Techniques: A Children's Oncology Group Survey.

PURPOSE: The aim of this study was to examine current practice patterns in pediatric total body irradiation (TBI) techniques among COG member institutions. METHODS AND MATERIALS: Between November 2019 and February 2020, a questionnaire containing 52 questions related to the technical aspects of TBI was sent to medical physicists at 152 COG institutions. The questions were designed to obtain technical information on commonly used TBI treatment techniques. Another set of 9 questions related to the clinical management of patients undergoing TBI was sent to 152 COG member radiation oncologists at the same institutions. RESULTS: Twelve institutions were excluded because TBI was not performed in their institutions. A total of 88 physicists from 88 institutions (63% response rate) and 96 radiation oncologists from 96 institutions (69% response rate) responded. The anterior-posterior/posterior-anterior (AP/PA) technique was the most common technique reported (49 institutions [56%]); 44 institutions (50%) used the lateral technique, and 14 (16%) used volumetric modulated arc therapy or tomotherapy. Midplane dose rates of 6 to 15 cGy/min were most commonly used. The most common specification for lung dose was the midlung dose for both AP/PA techniques (71%) and lateral techniques (63%). Almost all physician responders agreed with the need to refine current TBI techniques, and 79% supported the investigation of new TBI techniques to further lower the lung dose. CONCLUSIONS: There was no consistency in the practice patterns, methods for dose measurement, and reporting of TBI doses among COG institutions. The lack of standardization precludes meaningful correlation between TBI doses and clinical outcomes including disease control and normal tissue toxicity. The COG radiation oncology discipline is currently undertaking several steps to standardize the practice and dose reporting of pediatric TBI using detailed questionnaires and phantom-based credentialing for all COG centers.

Gonadal-sparing total body irradiation with the use of helical tomotherapy for nonmalignant indications.

BACKGROUND: The aim was to demonstrate the feasibility and technique of gonadal sparing total body irradiation (TBI) with helical tomotherapy. Total body irradiation is a common part of the conditioning regimen prior to allogeneic stem cell transplantation. Shielding or dose-reduction to the gonads is often desired to preserve fertility, particularly in young patients undergoing transplant for non-malignant indications. Helical tomotherapy (HT) has been shown to be superior to traditional TBI delivery for organ at risk (OA R) doses and dose homogeneity. MATERIALS AND METHODS: We present two representative cases (one male and one female) to illustrate the feasibility of this technique, each of whom received 3Gy in a single fraction prior to allogeneic stem cell transplant for benign indications. The planning target volume (PTV) included the whole body with a subtraction of OA Rs including the lungs, heart, and brain (each contracted by 1cm) as well as the gonads (testicles expanded by 5 cm and ovaries expanded by 0.5 cm). RESULTS: For the male patient we achieved a homogeneity index of 1.35 with a maximum and median planned dose to the testes of 0.53 Gy and 0.35 Gy, respectively. In-vivo dosimetry demonstrated an actual received dose of 0.48 Gy. For the female patient we achieved a homogeneity index of 1.13 with a maximum and median planned dose to the ovaries of 1.66 Gy and 0.86 Gy, respectively. CONCLUSION: Gonadal sparing TBI is feasible and deliverable using HT in patients with non-malignant diseases requiring TBI as part of a pre-stem cell transplant conditioning regimen.

Neurosurgical management of perineural metastases: A case series and review of the literature.

BACKGROUND: Perineural invasion (PNI) and spread are one of the grimmest prognostic factors associated with primary skin and head-and-neck cancers, yet remain an often confused, and underreported, phenomenon. Adding complexity to reaching a diagnosis and treating perineural spread (PNS) is the finding that patients may have no known primary tumor, history of skin cancer, and/or incidental PNI in the primary tumor. These delays in diagnosis and treatment are further compounded by an already slow disease process and often require multidisciplinary care with combinations of stereotactic radiosurgery, surgical resection, and novel treatments such as checkpoint inhibitors. METHODS: Six patients with metastatic cancer to the cranial nerves who underwent Gamma Knife radiosurgery (GKRS) treatment were chosen for retrospective analysis. This information included age, gender, any past surgeries (both stereotactic and regular surgery), dose of radiation and volume of the tumor treated in the GKRS, date of PNS, comorbidities, the patient follow-up, and pre- and post-GKRS imaging. The goal of the follow-up with radiographing imaging was to assess the efficacy of GKSS. RESULTS: The clinical course of six patients with PNS is presented. Patients followed variable courses with mixed outcomes: two patients remain living, one was lost to follow-up, and three expired with a median survival of 12 months from date of diagnosis. Patients at our institution are ideally followed for life. CONCLUSION: Given the morbidity and mortality of PNS of cancer, time is limited, and further understanding is required to improve outcomes. Here, we provide a case series of patients with PNS treated with stereotactic radiosurgery, discuss their clinical courses, and review the known literature.

History and current perspectives on the biological effects of high-dose spatial fractionation and high dose-rate approaches: GRID, Microbeam & FLASH radiotherapy.

The effects of various forms of ionising radiation are known to be mediated by interactions with cellular and molecular targets in irradiated and in some cases non-targeted tissue volumes. Despite major advances in advanced conformal delivery techniques, the probability of normal tissue complication (NTCP) remains the major dose-limiting factor in escalating total dose delivered during treatment. Potential strategies that have shown promise as novel delivery methods in achieving effective tumour control whilst sparing organs at risk involve the modulation of critical dose delivery parameters. This has led to the development of techniques using high dose spatial fractionation (GRID) and ultra-high dose rate (FLASH) which have translated to the clinic. The current review discusses the historical development and biological basis of GRID, microbeam and FLASH radiotherapy as advanced delivery modalities that have major potential for widespread implementation in the clinic in future years.

Dose cluster model parameterization of the parotid gland in irradiation of head and neck cancer.

To explore the parotid normal tissue complication probability (NTCP) modeling with percolation-based dose clusters for head-and-neck patients receiving concomitant chemotherapy and radiation therapy. Cluster models incorporating the spatial dose distribution in the parotid gland were developed to evaluate the radiation induced complication. Cluster metrics including the mean cluster size (NMCS) and the largest cluster size both normalized by the gland volume (NSLC) were evaluated and scrutinized against the benchmark NTCP. Two fitting strategies to the Lyman-Kutcher-Burman (LKB) model using the maximum likelihood method were devised: the volume parameter n fixed at 1.0 (mean dose model) and unrestricted (full LKB model). The fitted parameters TD50 and m were assessed with the LKB NTCP models with the available xerostomia data. NSLC was a better metric than NMCS with reference to the LKB model and strong correlation (r ~ 0.95) was observed between NTCP and NSLC. The mean dose model returned the parameter TD50 (39.9 Gy) and m (0.4) from the NSLC of threshold dose at around 40 Gy. Drastically different TD50 and m values were obtained from the fittings via the full LKB model, where the threshold dose would be near 27 Gy. Bootstrapping analyses further confirmed the fitting outcomes. Strong correlation with the traditional NTCP models revealed that the cluster model could achieve what NTCP models attain and may offer additional information. Parameterization of the model indicated that the model could have different predictions from current clinical recommendations. Further investigation using toxicity data is under way to validate the cluster model.

Radiosurgery for mesial temporal lobe epilepsy following ROSE trial guidelines - A planning comparison between Gamma Knife, Eclipse, and Brainlab.

PURPOSE: This study aims to compare stereotactic radiosurgery (SRS) planning of epilepsy that complies with Radiosurgery or Open Surgery for Epilepsy (ROSE) guidelines in GammaKnife, non-coplanar conformal (NCC) plan in Eclipse, dynamic conformal arc (DCA) plan in Brainlab, and a volumetric modulated arc therapy (VMAT) plan in Eclipse. METHODS: Twenty plans targeting Mesial temporal lobe epilepsy (MTLE) was generated using GammaKnife, Eclipse with 20 NCC beams, Brainlab with 5 DCA, and Eclipse VMAT with 4 arcs observing ROSE trial guidelines. Multivariate analysis of variance and Wilcoxon signed-rank test were used to compare dosimetric data of the plans and perform pairwise comparison, respectively. RESULTS: The plans obeyed the recommended prescription isodose volume (PIV) within 5.5-7.5 cc and maximum doses to brainstem, optic apparatus (OA) of 10 and 8 Gy, respectively, for a prescription dose of 24 Gy. The volumes of the target were in the range 4.0-7.4 cc. Mean PIV, maximum dose to brainstem, OA were 6.5 cc, 10 Gy, 7.9 Gy in GammaKnife; 7.2 cc, 6.1 Gy, 4.5 Gy in Eclipse NCC; 7.2 cc, 6.4 Gy, 5.7 Gy in Brainlab DCA; and 5.2 cc, 8.4 Gy, 6.1 Gy in Eclipse VMAT plans, respectively. Multivariate analysis of variance showed significant differences among the 4 SRS planning techniques (P-values < 0.01). CONCLUSIONS: Among the 4 SRS planning methods, VMAT with least PIV and acceptable maximum doses to brainstem and OA showed highest compliance with ROSE trial. Having the most conformal dose distribution and least dose inhomogeneity, VMAT scored higher than GK, Eclipse NCC, and Brainlab DCA plans.

A Dose Falloff Gradient Study in RapidArc Planning of Lung Stereotactic Body Radiation Therapy.

INTRODUCTION: Radiation Therapy Oncology Group (RTOG) report #0813 and 0915 recommends using D2cm and R50% as plan quality metrics for evaluation of normal tissue sparing in stereotactic body radiation therapy (SBRT) of lung lesion. This study introduces dose falloff gradient (DFG) as a tool for analyzing the dose beyond the planning target volume (PTV) extending into normal tissue structures. In ascertaining the impact of PTV size and SBRT planning techniques in DFG, this study questions the independence of the RTOG recommended metrics. MATERIALS AND METHODS: In this retrospective study, 41 RapidArc lung SBRT plans with 2 or 3 complete or partial arcs were analyzed. PTV volumes ranged between 5.3 and 113 cm3 and their geographic locations were distributed in both lungs. 6MV, 6 MV-FFF, 10 MV, or 10 MV-FFF energies were used. RTOG-0915 metrics conformity index, homogeneity index, D2cm, R50%, and HDloc were evaluated. DFG was computed from the mean and maximum dose in seven concentric 5 mm wide rings outside the PTV. DFG was investigated against the volume of normal lung irradiated by 50% isodose volume. Treatment plans with alternate energy and couch rotations were generated. RESULTS: The dose falloff beyond PTV was modeled using a double exponential fit and evaluated for relationship with intermediate lung dose. Photon energy and beam configuration had a minimal impact on the dose falloff outside. The product of normalized D2cm and R50% was estimated to have a slowly varying value. CONCLUSIONS: Dose falloff outside PTV has been studied as a function of radial distance and ascertained by intermediate dose to normal lung. DFG can serve as a complementary plan quality metric.

Three-dimensional cluster formation and structure in heterogeneous dose distribution of intensity modulated radiation therapy.

PURPOSE: To investigate three-dimensional cluster structure and its correlation to clinical endpoint in heterogeneous dose distributions from intensity modulated radiation therapy. METHODS: Twenty-five clinical plans from twenty-one head and neck (HN) patients were used for a phenomenological study of the cluster structure formed from the dose distributions of organs at risks (OARs) close to the planning target volumes (PTVs). Initially, OAR clusters were searched to examine the pattern consistence among ten HN patients and five clinically similar plans from another HN patient. Second, clusters of the esophagus from another ten HN patients were scrutinized to correlate their sizes to radiobiological parameters. Finally, an extensive Monte Carlo (MC) procedure was implemented to gain deeper insights into the behavioral properties of the cluster formation. RESULTS: Clinical studies showed that OAR clusters had drastic differences despite similar PTV coverage among different patients, and the radiobiological parameters failed to positively correlate with the cluster sizes. MC study demonstrated the inverse relationship between the cluster size and the cluster connectivity, and the nonlinear changes in cluster size with dose thresholds. In addition, the clusters were insensitive to the shape of OARs. CONCLUSION: The results demonstrated that the cluster size could serve as an insightful index of normal tissue damage. The clinical outcome of the same dose-volume might be potentially different.

Robust optimization in lung treatment plans accounting for geometric uncertainty.

Robust optimization generates scenario-based plans by a minimax optimization method to find optimal scenario for the trade-off between target coverage robustness and organ-at-risk (OAR) sparing. In this study, 20 lung cancer patients with tumors located at various anatomical regions within the lungs were selected and robust optimization photon treatment plans including intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were generated. The plan robustness was analyzed using perturbed doses with setup error boundary of ±3 mm in anterior/posterior (AP), ±3 mm in left/right (LR), and ±5 mm in inferior/superior (IS) directions from isocenter. Perturbed doses for D99 , D98 , and D95 were computed from six shifted isocenter plans to evaluate plan robustness. Dosimetric study was performed to compare the internal target volume-based robust optimization plans (ITV-IMRT and ITV-VMAT) and conventional PTV margin-based plans (PTV-IMRT and PTV-VMAT). The dosimetric comparison parameters were: ITV target mean dose (Dmean ), R95 (D95 /Dprescription ), Paddick's conformity index (CI), homogeneity index (HI), monitor unit (MU), and OAR doses including lung (Dmean , V20 Gy and V15 Gy ), chest wall, heart, esophagus, and maximum cord doses. A comparison of optimization results showed the robust optimization plan had better ITV dose coverage, better CI, worse HI, and lower OAR doses than conventional PTV margin-based plans. Plan robustness evaluation showed that the perturbed doses of D99 , D98 , and D95 were all satisfied at least 99% of the ITV to received 95% of prescription doses. It was also observed that PTV margin-based plans had higher MU than robust optimization plans. The results also showed robust optimization can generate plans that offer increased OAR sparing, especially for normal lungs and OARs near or abutting the target. Weak correlation was found between normal lung dose and target size, and no other correlation was observed in this study.