Time motion study to evaluate the impact of flattening filter free beam on overall treatment time for frameless intracranial radiosurgery using Varian TrueBeam® linear accelerator

BackgroundThe aim was to study the impact of the flattening filter free (FFF) beam on overall treatment time for frameless intracranial radiosurgery using TrueBeam^® LINAC.The development of frameless stereotactic radiosurgery (SRS) is possible due to the incorporation of image guidance in the delivery of treatment. It is important to analyze the cost and benefits of FFF beams for treating SRS by understanding the impact of FFF beams in reducing the treatment time.Materials and methodsDynamic conformal arc (DCA ) and volumetric arc therapy (VMAT) plans were generated using 6 MV with a flattening filter (FF) and FFF beams. Overall treatment time was divided into beam on time (BOT) and beam off time (BFT). Percentage beam on time reduction (PBOTR) and Percentage total time reduction (PTTR) factors were defined for the comparison.ResultsBOT reduction was observed to be significant for higher dose per fraction but subjected to the treatment technique and modulation differences. PBOTR values are much higher than PTTR values. The 39.9% of PBOTR resulted in only 8% PTTR for DCA and 65.3% resulted in 15.9% PTTR for VMAT.ConclusionMajor BFT was utilized for imaging and verification. FFF beam significantly reduced the beam on time and was found to be most effective if the fractional dose was as high as that for SRS. Newly defined PBOTR and PTTR factors are very useful indicators to evaluate the efficacy of FFF beams in terms of time reduction.     

Evaluation of intrafractional head motion for intracranial stereotactic radiosurgery with a thermoplastic frameless mask and ceiling-floor-mounted image guidance device

PurposeTo evaluate intrafractional head motion (IFM) in patients who underwent intracranial stereotactic radiosurgery with the ExacTrac X-ray system (ETX) and a frameless mask.MethodsA total of 143 patients who completed a pre-treatment examination for IFM were eligible for this study. The frameless mask type B R408 (Klarity Medical & Equipment Co., Ltd., Guangzhou, China), which covers the back of the head, and the entire face, was used for patient immobilization. After the initial 6D correction and first X-ray verification (IFM₁), X-ray verification was performed every 3 min for a duration of 15 min. The IFM_p (2 ≤ p ≤ 6) was calculated as the positional difference from IFM₁. In addition, the inter-phase IFM (IP-IFM) and IFM_m were calculated. The IP-IFM was defined as |IFM_p − IFM_p-1|, and IFM_m as the difference between the values after all patients were asked to move their heads intentionally with the frameless mask on.ResultsBoth translational IFM_p and IP-IFM exceeded 1 mm for a single patient, whereas, for all patients, the translational IFM_m values were kept to within 1 mm in all directions. The proportions of the rotational IFM_p, IP-IFM, and IFM_m values within 0.5° were greater than 94.4%, 98.6%, and 90.2% for all of the rotational axes, respectively.ConclusionsA frameless mask achieved highly accurate patient positioning in combination with ETX and a 6°-of-freedom robotic couch; however, a deviation over 1 mm and 0.5° was observed with low frequency. Therefore, X-ray verification and correction are required during treatment.     

Dosimetric and localization accuracy of Elekta high definition dynamic radiosurgery

Background and PurposeWith the increasingly prominent role of stereotactic radiosurgery in radiation therapy, there is a clinical need for robust, efficient, and accurate solutions for targeting multiple sites with one patient setup. The end-to-end accuracy of high definition dynamic radiosurgery with Elekta treatment planning and delivery systems was investigated in this study.Materials and MethodsA patient-derived CT scan was used to create a radiosurgery plan to seven targets in the brain. Monaco was used for treatment planning using 5 VMAT non-coplanar arcs. Prior to delivery, 3D-printed phantoms from RTsafe were ordered including a gel phantom for 3D dosimetry, phantom with 2D film insert, and an ion chamber phantom for point dose measurement. Delivery was performed using the Elekta VersaHD, XVI cone-beam CT, and HexaPOD six degree of freedom tabletop.ResultsAbsolute dose accuracy was verified within 2%. 3D global gamma analysis in the film measurement revealed 3%/2 mm passing rates >95%. Gel dosimetry 3D global gamma analysis (3%/2 mm) were above 90% for all targets with the exception of one. Results were indicative of typical end-to-end accuracies (<1 mm spatial uncertainty, 2% dose accuracy) within 4 cm of isocenter. Beyond 4 cm, 2 mm accuracy was found.ConclusionsHigh definition dynamic radiosurgery expands clinically acceptable stereotactic accuracy to a sphere around isocenter allowing for radiosurgery of several targets with one setup with a high degree of dosimetric precision. Gel dosimetry proved to be an essential tool for the validation of the 3D dose distributions in this technique.     

Influence of multi-leaf collimator leaf width in radiosurgery via volumetric modulated arc therapy and 3D dynamic conformal arc therapy

PurposeTo study the influence of Multileaf Collimator (MLC) leaf width in radiosurgery treatment planning for Volumetric Modulated Arc Therapy (VMAT) and 3D Dynamic Conformal Arc Therapy (3D-DCA).Material and methods16 patients with solitary brain metastases treated with radiosurgery via the non-coplanar VMAT were replanned for the 3D-DCA. For each planning technique two MLC leaf width sizes were utilized, i.e. 5 mm and 2.5 mm. These treatment plans were compared using dosimetric indices (conformity, gradient and mean dose for brain tissue) and the normal tissue complication probability (NTCP).ResultsAn improvement in planning quality for VMAT was observed versus 3D-DCA for any MLC leaf width, mainly with regards to dose conformity and to a lesser extent regards dose gradient. No significant difference was observed for any of both techniques using smaller leaf width. However, dose gradient was improved in favor of the 2.5 mm MLC for either of both techniques (15% VMAT and 10% 3D-DCA); being noticeable for lesions smaller than 10 cm³. Nonetheless, the NTCP index was not significantly affected by variations in the dose gradient index.ConclusionsThis, our present study, suggests that the use of an MLC leaf width of 2.5 mm via the noncoplanar VMAT and 3D-DCA techniques provides improvement in terms of dose gradient for small volumes, over those results obtained with an MLC leaf width of 5 mm. The 3D-DCA does also benefit from MLC leaf widths of a smaller size, mainly in terms of conformity.     

Intérêt de la technique de détection du ganglion sentinelle appliquée aux cancers de l’utérus : à propos de trois cas

IntroductionThe sentinel node technique (SN) was proposed in cervical cancers in order to optimise the diagnosis of metastases and the lymphatic micrometastases in the early stages while avoiding useless wide clearings out. The identification of this node is done by injection of a dye and/or a radioactive colloid and its ablation for pathological examination.Patients and methodsWe report the case of three patients followed for a uterine cancer having benefitted from a lymphoscintigraphy before surgery. During the surgical procedure, the detection of the sentinel node was carried out after cervical injection of blue dye and using a gamma detection probe.ResultsThe lymphoscintigraphy was positive for two cases with a positive detection for the three cases during the operation. The pathological study revealed a node metastasis for one case. The technical of the sentinel node applied to uterine cancers appears realizable essentially for uterine cancers of early stage (I). However the risk of false negative can be observed in advanced cancer (III), as it is the case of our patient having a negative lymphoscintigraphy.ConclusionThe nuclear medicine is important in the detection of the sentinel node of various cancers, uterine cancer included, thus allowing an appropriate cardiologic management.     

Feasibility and potential advantages using VMAT in SRS metastasis treatments

BackgroundUtilization of stereotactic radiosurgery (SRS) for brain metastases (BM) has become the technique of choice as opposed to whole brain radiation therapy (WBRT). The aim of this work is to evaluate the feasibility and potential benefits in terms of normal tissue (NT) and dose escalation of volumetric modulated arc therapy (VMAT) in SRS metastasis treatment. A VMAT optimization procedure has therefore been developed for internal dose scaling which minimizes planner dependence.Materials and methodsFive patient-plans incorporating treatment with frame-based SRS with dynamic conformal arc technique (DA) were re-planned for VMAT. The lesions selected were between 4–6 cm³. The same geometry used in the DA plans was maintained for the VMAT cases. A VMAT planning procedure was performed attempting to scale the dose in inner auxiliary volumes, and to explore the potential for dose scaling with this technique. Comparison of dose-volume histogram (DVH) parameters were obtained.ResultsVMAT allows a superior NT sparing plus conformity and dose scaling using the auxiliary volumes. The VMAT results were significantly superior in NT sparing, improving both the V₁₀ and V₁₂ values in all cases, with a 2–3 cm³ saving. In addition, VMAT improves the dose coverage D₉₅ by about 0.5 Gy. The objective of dose escalation was achieved with VMAT with an increment of the Dmean and the Dmedian of about 2 Gy.ConclusionsThis work shows a benefit of VMAT in SRS treatment with significant NT sparing. A VMAT optimization procedure, based on auxiliary inner volumes, has been developed, enabling internal dose escalation.     

Radiation dose to the fetus during CyberKnife radiosurgery for a brain tumor in pregnancy

PurposePregnancy during radiosurgery is extremely rare in clinical practice. We report fetal dose results during CyberKnife radiosurgery for a brain tumor in pregnancy.Methods and materialsA 26 year old pregnant woman with a rapidly growing deep-seated grade-III glioma was treated during the third trimester of gestation using CyberKnife. Ultrasound imaging was used to determine the position of the embryo prior to treatment. A dose of 1400 cGy was prescribed aiming to control tumor growth until delivery of the child. Prior to radiosurgery, the treatment was simulated on an anthropomorphic phantom. Radiation dose to the embryo was measured using a Farmer chamber and EBT3 films.ResultsFetal doses of 4.4 cGy and 4.1 cGy were measured for the embryo's head and legs, lying at 56 cm and 72 cm from the isocenter, respectively, using the Farmer chamber situated at 8.5 cm depth beneath the phantom surface. Dose results of 4.4 cGy, 3.5 cGy and 2.0 cGy were measured with the films situated at depths of 6.5 cm, 9.5 cm and 14.5 cm, respectively. An average dose of 4.2 cGy to the fetus was derived from the above values. A corresponding dose of 3.2 cGy was also calculated based on results obtained using EBT3 films situated upon the patient skin.ConclusionsThe measured fetal doses are below the threshold of 10 cGy for congenital malformations, mental and growth retardation effects. The radiogenic cancer risk to the live-born embryo was estimated less than 0.3% over the normal incidence. The treatment was administered successfully, allowing the patient to deliver a healthy child.     

A case report of stereotactic radiosurgery in a patient with Ehlers–Danlos syndrome

In this report, we outline the case of a patient who has Ehlers–Danlos Syndrome (EDS) who received two courses of CyberKnife stereotactic radiosurgery (SRS) for metastatic non-small cell lung cancer. Patients with EDS have increased blood vessel fragility, and therefore are subject to increased risk of bleeding. There are no published data regarding the risks of hemorrhage associated with SRS for intracranial metastases in this patient population. The patient described in this case report had two courses of SRS for two sites of brain metastases. She tolerated treatment well, with no acute toxicity and good local control to date. We have also included a discussion of published literature regarding toxicity of intracranial radiation in patients with EDS.     

Initial evaluation of intrafraction motion using frameless CyberKnife VSI system

Aim

To analyze intrafraction movement in patients undergoing frameless robotic radiosurgery and evaluate the influence of image acquisition frequency on global accuracy.

Background

Stereotactic radiosurgery requires high spatial accuracy in dose delivery. In conventional radiosurgery, a rigid frame is used to guarantee a correct target alignment and no subsequent movement. Frameless radiosurgery with thermoplastic mask for immobilization cannot completely eliminate intrafraction patient movement. In such cases, it is necessary to evaluate its influence on global treatment accuracy.

Materials and methods

We analyzed the intrafraction motion of the first 15 patients undergoing intracranial radiosurgery (39 fractions) with the CyberKnife VSI system at our institution. Patient position was measured at a 15–90-s interval and was used to estimate intrafraction patient movement.

Results

With our acquisition image protocol and immobilization device, the 99% displacement error was lower than 0.85 mm. The systematic movement components were lower than 0.05 mm and the random component was lower than 0.3 mm in the 3 translational axes. Clear linear time dependence was found in the random component.

Conclusions

Selection of the X-ray image acquisition time is necessary to meet the accuracy required for radiosurgery procedures with the CyberKnife VSI system. We verified that our image acquisition protocol met the 1-mm criterion.     

Local failure after primary radiotherapy in lung cancer: Is there a role for SBRT?

AimOur purpose is to construe the role of stereotactic body radiation therapy (SBRT) in the management of lung cancer from our early experience with SBRT for salvage treatment in patients with recurrent lung cancer after initial radiation therapy.BackgroundLocoregional recurrences are a frequent challenge in patients treated with radio-chemotherapy for locally advanced NSCLC. Conventional external beam radiation therapy (EBRT) is rarely given as salvage treatment because of the risk of toxicity. There is a paucity of published studies evaluating the role of SBRT in this clinical setting.Materials and methodsBetween 2008 and present, 10 patients with biopsy proven non-small cell lung cancer (NSCLC) underwent 14 radiosurgical procedures for salvage therapy after failing initial radiation treatment. Patients’ age ranged from 54 to 88 years with a median of 74 years in 6 males and 4 females. Intervals from initial radiation treatment to salvage SBRT were 3–33 months with a median of 13 months. SBRT treatments were delivered using Intensity Modulated Volumetric Arc Therapy (VMAT). All patients received concomitant chemotherapy.ResultsOverall survival after salvage radiosurgery ranged from 6 to 41 months (mean 20 months, median 18 months). Four of the ten patients are alive with disease locally controlled. Of the remaining 6 patients, 4 had distant progression of disease with brain metastases and one had both brain and lung metastases. The other patient had a regional failure. Toxicities were found in three of the ten (30%) patients with grade I pneumonitis.ConclusionIn our early experience, salvage SBRT is an effective modality of treating patients who failed after conventional irradiation, achieving excellent results in terms of local control with acceptable toxicity. Further prospective studies are needed to determine optimal fractionation schemes.     

Investigating the spatial accuracy of CBCT-guided cranial radiosurgery: A phantom end-to-end test study

PurposeTo evaluate the spatial accuracy of a frameless cone-beam computed tomography (CBCT)-guided cranial radiosurgery (SRS) using an end-to-end (E2E) phantom test methodology.Methods and materialsFive clinical SRS plans were mapped to an acrylic phantom containing a radiochromic film. The resulting phantom-based plans (E2E plans) were delivered four times. The phantom was setup on the treatment table with intentional misalignments, and CBCT-imaging was used to align it prior to E2E plan delivery. Comparisons (global gamma analysis) of the planned and delivered dose to the film were performed using a commercial triple-channel film dosimetry software. The necessary distance-to-agreement to achieve a 95% (DTA95) gamma passing rate for a fixed 3% dose difference provided an estimate of the spatial accuracy of CBCT-guided SRS. Systematic (∑) and random (σ) error components, as well as 95% confidence levels were derived for the DTA95 metric.ResultsThe overall systematic spatial accuracy averaged over all tests was 1.4 mm (SD: 0.2 mm), with a corresponding 95% confidence level of 1.8 mm. The systematic (Σ) and random (σ) spatial components of the accuracy derived from the E2E tests were 0.2 mm and 0.8 mm, respectively.ConclusionsThe E2E methodology used in this study allowed an estimation of the spatial accuracy of our CBCT-guided SRS procedure. Subsequently, a PTV margin of 2.0 mm is currently used in our department.     

Evaluation of results of linac-based radiosurgery for brain metastases from primary lung cancer

Aim

The purpose of our review was to evaluate results of radiosurgery for patients with brain metastases from lung cancer.

Background

Lung cancer is the leading cause of death from cancer and the most common source of brain metastases. Radiosurgery allows the precise focal delivery of a high single radiation dose to brain metastases and results in high rates of local control.

Materials and methods

83 patients were treated between 2006 and 2008. We evaluated local control and outcome after radiosurgery and identified prognostic factors.

Results

Median survival in the whole group was 7.8 months from radiosurgery and 11 months from diagnosis. Median survival in classes I, II and III was 13.2, 8.2 and 2.2 months. For 94% of patients symptoms improved or stabilised at the first follow-up visit and this status did not change during 7.1 months. According to the univariate analysis, factors associated with improved survival included: RPA class 1 compared with RPA 2 and 3, RPA class 2 compared with RPA 3, KPS > 70, control of the primary disease, radiosurgery performed more than once, level of haemoglobin >7 mmol/1, absence of extracranial metastases, volume of the biggest lesion <11 cm³. The multivariate analysis confirmed a significant influence on survival for the following factors: RPA class 1 as compared with RPA 3, KPS > 70, absence of extracranial metastases, multiplicity of radiosurgery.

Conclusions

Stereotactic radiosurgery is a safe and effective treatment. It proved to be effective and safe in older patients. Selection of patients who are likely to benefit most should be based on prognostic factors. KPS proved to be the most important prognostic factor. In the RPA III group (patients with KPS < 70) survival time was similar to that achieved after symptomatic medical management.     

On the evaluation of edgeless diode detectors for patient-specific QA in high-dose stereotactic radiosurgery

PurposeIn this work, the potential of an innovative “edgeless” silicon diode was evaluated as a response to the still unmet need of a reliable tool for plan dosimetry verification of very high dose, non-coplanar, patient-specific radiosurgery treatments. In order to prove the effectiveness of the proposed technology, we focused on radiosurgical treatments for functional disease like tremor or pain.MethodsThe edgeless diodes response has been validated with respect to clinical practice standard detectors by reproducing the reference dosimetry data adopted for the Treatment Planning System. In order to evaluate the potential for radiosurgery patient-specific treatment plan verification, the anthropomorphic phantom Alderson RANDO has been adopted along with three edgeless sensors, one placed in the centre of the Planning Target Volume, one superiorly and one inferiorly.ResultsThe reference dosimetry data obtained from the edgeless detectors are within 2.6% for output factor, off-axis ratio and well within 2% for tissue phantom ratio when compared to PTW 60,018 diode. The edgeless detectors measure a dose discrepancy of approximately 3.6% from the mean value calculated by the TPS. Larger discrepancies are obtained in very steep gradient dose regions when the sensors are placed outside the PTV.ConclusionsThe angular independent edgeless diode is proposed as an innovative dosimeter for patient quality assurance of brain functional disorders and other radiosurgery treatments. The comparison of the diode measurements with TPS calculations confirms that edgeless diodes are suitable candidates for patient-specific dosimetric verification in very high dose ranges delivered by non-isocentric stereotactic radiosurgery modalities.     

Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol

IntroductionUp to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates.MethodsThis study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0−2 cm lesions, 14 Gy for 2.1−3 cm lesions, and 12 Gy for 3.1−4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90−05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria.DiscussionThis study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population.Trial RegistrationClinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).     

Predictive biochemical-markers for the development of brain metastases from lung cancer: Clinical evidence and future directions

BackgroundBrain metastases are a common complication of patients with lung cancer and lung cancer is one of the most common causes of brain metastases. The occurrence of brain metastases is associated with poor prognosis and high morbidity, even after intensive multimodal therapy. Therefore, identifying lung cancer patients with who are at high risk of developing brain metastases and applying effect intervention is important to reduce or delay the incidence of brain metastases. Biochemical-markers may meet an unmet need for following patients’ mechanisms of brain metastases.MethodsData for this review were identified by searches of Pubmed and Cochrane databases, and references from relevant articles using the search terms “lung cancer” and “brain metastasis”. Meeting abstracts, unpublished reports and review articles were not considered.ResultsClinical results for pathological and circulating markers including cancer molecular subtypes, miRNA, single nucleotide polymorphisms, and other markers are presented. However, these biochemical-markers are not yet established surrogate assessments for prediction of brain metastases.ConclusionsBiochemical-markers reported allowed physicians to identify which patients with lung cancer are at high risk for brain metastases. Prospective randomized clinical studies are needed to further assess the utility of these biochemical-markers.     

The effect of fractionated gamma knife radiosurgery on visual acuity in patients with optic nerve tumor

BackgroundStereotactic radiosurgery (SRS) method has been considered the first-line treatment option to treat patients involved with pre-optic nerve tumors. However, studies have shown that using fractionated SRS, normal tissue sparing and tumor dose can be strongly increased simultaneously. Our main goal was to illustrate the effects of fractionated SRS approach in optic nerve tumor treatment and its adjacent sensitive structures.Materials and methods19 patients involved in optic nerve tumor with clinical symptoms of vision loss were treated with Gamma Knife radiosurgery in three sessions with 12 hours intervals between them. The prescribed dose was about 6.0 ± 1.2 Gy. Patient-related parameters including pre-treatment and after-treatment tumor size, visual acuity and visual field were evaluated using the Snell chart and MRI imaging. Patients were followed for about 14 months.ResultThe overall result showed vision improvement for patients with low and moderate visual loss. However, there was no significant improvement in patients with severe visual loss. Relative improvement was observed in blind patients, although poorly. There was no evidence of growth, recurrence, or new tumor after treatment in patients.ConclusionFractionated gamma knife radiosurgery offers a safe and effective alternative for benign lesions adjacent to the optic nerve.     

Anidulafungin versus fluconazole in the treatment of Candida albicans chorioretinitis

BackgroundCandida albicans chorioretinitis is the most common cause of endogenous fungal endophthalmitis. Echinocandins are recommended as first-line therapy in the treatment of invasive candidiasis (IC), but in clinically stable patients with IC and endophthalmitis caused by Candida species susceptible to azole compounds these are the first-line treatment due to their better intraocular penetration.Case reportA 42-year-old woman admitted to hospital for duodenal perforation after gastrointestinal surgery and treated with broad-spectrum antibiotics developed C. albicans candidemia. According to protocol, an antifungal treatment with anidulafungin was given. The patient presented no visual symptoms but on routinary ophthalmoscopic examination multiple bilateral chorioretinal lesions were observed. Systemic therapy was changed to fluconazole, with good systemic and ocular results.ConclusionsAzole compounds are the first-line therapy for endophthalmitis associated with candidemia. However, clinical guidelines often propose echinocandins as the first option for IC. In some cases, C. albicans chorioretinitis will require a change in the systemic treatment to assure better intraocular penetration. According to the current evidence and our own experience, routine funduscopy is not necessary in all IC patients. However, we do recommend fundus examination in patients with visual symptoms or those unable to report them (paediatric patients and patients with an altered level of consciousness), and in those who are being treated with echinocandins in monotherapy.