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.

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.

Pulsed reduced dose-rate radiotherapy for previously irradiated tumors in the brain and spine.

BACKGROUND: Patients with unresectable locoregional cancer recurrences have limited management options. Reirradiation increases the risk of toxicity, particularly when perilesional dose-volume constraints are exceeded. We present and discuss two cases of previously irradiated tumors in the central nervous system (CNS) that was reirradiated using the pulsed reduced dose-rate radiotherapy (PRDR) technique. CASE DESCRIPTION: A 58-year-old female with a history of metastatic small cell lung cancer to the brain status post multiple rounds of radiation and chemotherapy presented with increasing weakness in her right arm and leg. Magnetic resonance imaging (MRI) revealed a growly peripherally enhancing 1.2 cm mass in the left precentral gyrus that had previously received prophylactic cranial irradiation and stereotactic radiosurgery. The patient was re-irradiated with 35 Gy in 100 fractions over 3 weeks, using PRDR with improved motor function at 3-month follow-up. A 41-year-old male with recurrent glioblastoma of the thoracic spinal cord presented with worsening neurological symptoms, including inability to ambulate due to bilateral leg weakness, causing wheelchair use. MRI thoracic spine revealed a recurrent thoracic lesion 2.2 × 1 × 0.8 cm. In addition to chronic chemotherapy, the patient was retreated palliatively in the same area at 50 Gy in 250 fractions, over 6 weeks, using PRDR. The treated lesion was stable on follow-up imaging, and the patient was able to walk with the assistance of a walker. CONCLUSION: In our two cases, PRDR proved effective in the treatment of recurrent malignant CNS tumors that were previously irradiated. Prospective studies are needed to delineate the efficacy and toxicity of PRDR.

Evidence for Early Stage Anti-Tumor Immunity Elicited by Spatially Fractionated Radiotherapy-Immunotherapy Combinations.

The combination of radiotherapy and immunotherapy may generate synergistic anti-tumor host immune responses and promote abscopal effects. Spatial fractionation of a radiation dose has been found to promote unique physiological responses of tumors, which might promote synergy with immunotherapy. To determine whether spatial fractionation may augment immune activity, whole-tumor or spatial fractionation grid radiation treatment (GRID) alone or in combination with antibodies against immune checkpoints PD1 and CTLA-4 were tested in an immunocompetent mouse model using a triple negative breast tumor (4T1). Tumor growth delay, immunohistochemistry and flow cytometry were used to characterize the effects of each treatment type. Whole-beam radiation with immune checkpoint inhibition significantly restrained tumor growth in the irradiated tumor, but not abscopal tumors, compared to either of these treatments alone. In mice that received spatially fractionated irradiation, evidence of abscopal immune responses were observed in contralateral tumors with markedly enhanced infiltration of both antigen-presenting cells and activated T cells, which were preceded by increased systemic IFNγ production and led to eventual tumor growth delay. These studies suggest that systemic immune activation may be triggered by employing GRID to a primary tumor lesion, promoting anti-tumor immune responses outside the treatment field. Interestingly, PD-L1 was found to be upregulated in abscopal tumors from GRID-treated mice. Combined radio-immunotherapy therapy is becoming a validated and novel approach in the treatment of cancer. With the potential increased benefit of GRID to augment both local and metastatic disease responses, further exploration of GRID treatment as a part of current standards of care is warranted.

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.

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.

Polymer gel dosimetry by nuclear Overhauser enhancement (NOE) magnetic resonance imaging.

The response to radiation of polymer gel dosimeters has previously been measured by magnetic resonance imaging (MRI) in terms of changes in the water transverse relaxation rate (R 2w) or magnetization transfer (MT) parameters. Here we report a new MRI approach, based on detecting nuclear Overhauser enhancement (NOE) mediated saturation transfer effects, which can also be used to detect radiation and measure dose distributions in MAGIC-f (Methacrylic and Ascorbic Acid and Gelatin Initiated by Copper Solution with formaldehyde) polymer gels. Results show that the NOE effects produced by low powered radiofrequency (RF) irradiation at specific frequencies offset from water may be quantified by appropriate measurements and over a useful range depend linearly on the radiation dose. The NOE effect likely arises from the polymerization of methacrylic acid monomers which become less mobile, facilitating dipolar through-space cross-relaxation and/or relayed magnetization exchange between polymer and water protons. Our study suggests a potential new MRI method for polymer gel dosimetry.

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.

Technical Note: A planning technique to lower normal tissue toxicity in lung SBRT plans based on two likely dependent RTOG metrics.

PURPOSE: Intermediate- and low-dose falloff in stereotactic body radiotherapy (SBRT) of lung tumor is known to relate to normal tissue toxicity. The purpose is twofold to analyze the relation between RTOG parameters (namely, R50%, D2cm) in lung SBRT plans and to explore planning methods that correlate with higher than acceptable dose to normal tissue. METHODS: RTOG recommended target dose coverage, conformity index, homogeneity index, R50%, and D2cm were evaluated retrospectively in 105 lung tumor SBRT plans. Deviations in R50% and D2cm were correlated with parameters including prescription dose, tumor location, number of beams or arcs, beam configuration (coplanar or noncoplanar), type of treatment plan (3D-CRT, IMRT or volumetric arc therapy), and shortest distance to the chest wall. RESULT: All plans met the target coverage, conformity index, homogeneity index, and critical organ dose tolerance objectives. Dose falloff product (DFP) of R50% and D2cm has a small variance and small dependence on PTV. Low correlation between DFP and PTV suggests that R50% and D2cm are not independent. Coplanar beam placement was found to be prevalent among plans with large deviations in R50%, D2cm. CONCLUSION: This study questions the independence of the two RTOG recommended metrics, R50% and D2cm in lung SBRT plans, and suggests that noncoplanar beams may provide better normal tissue sparing by reducing the intermediate dose falloff.

Metodologia para dosimetria de campos de radiaçäo X - nível radioterapia - utilizando Sistemas Tandem de câmaras de ionizaçäo comerciais / Methodology for X radiation beam dosimetry - radiotherapy level - using Tandem systems of commercial ionization chambers

Para a utilizaçäo dos campos de radiaçäo X nas clínicas de radioterapia e nos laboratórios de calibraçäo de detectores de radiaçäo é necessário o conhecimento de suas características e o controle periódico do desempenho das câmaras de ionizaçäo utilizadas nas medidas. Neste trabalho é apresentada uma metodologia para a utilizaçäo do sistema Tandem, de forma rotineira, na dosimetria dos feixes de radiaçäo X - nível radioterapia - em substituiçäo ao procedimento rotineiro convencional de determinaçäo de camadas semi-redutoras utilizando-se absorvedores. A grande vantagem deste método se deve ao fato de ser um procedimento simples e rápido e com resultados equivalentes à dosimetria realizada pela metodologia convencional.

Comparaçäo entre sistemas Tandem para raios-x de baixas energias / Comparison between Tandem system to x-rays of low energy

Sistemas Tandem, constituídos por pares de câmaras comerciais e por um par de câmaras de placas paralelas desenvolvidas no IPEN, foram testados em campos padrões de radiação X de baixa energias (14 a 21keV), para comparação de resultados.

Tandem systems using commercial ionization chambers as well as the parallelplates chambers developed at IPEN were tested in standard low energy X radiation fields (14 -21keV) for comparative purposes.