Intracranial chordoma: radiosurgery,hypofractionated stereotactic radiotherapy and treatment outcomes

BackgroundThe aim of the study was to assess the results of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy (SRS/SRT) for skull base chordomas.Materials and methodsTwenty-three patients aged 12–75 were treated with SRS/SRT due to skull base chordoma. In 19 patients SRS/SRT was a part of the primary therapy, while in 4, a part of the treatment of recurrence. In 4 patients SRS/SRT was used as a boost after conventional radiotherapy and in 19 cases it was the only irradiation method applied. Patients were irradiated to total dose of 6–35 Gy and median total equivalent dose of 52 Gy.ResultsDuring median follow-up of 39 months, 4 patients died. One-, two- and five-year OS was 95%, 89% and 69%, respectively. In nine patients, progression of the disease was diagnosed during study period. One-, two- and five-year progression free survival (PFS) from the end of radiotherapy was 81%, 59% and 43%, respectively. Radiotherapy was well tolerated and only two patients in our group experienced moderate treatment-related toxicity.ConclusionSRS/SRT alone or in combination with surgery is a safe and effective method of irradiation of patients with skull base chordomas. High EQD₂ is necessary to achieve satisfactory treatment results.     

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.     

Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer

BackgroundThis study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials.Materials and methodsThe National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS ). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling.ResultsOf 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2−, ER+/HER2+, ER−/HER2+, and ER−/HER2−, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER−/HER2+ and ER−/HER2− disease had worse OS than patients with ER+/HER2− disease, for both patients treated with SRS and for patients treated with WBRT.ConclusionsMolecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes.     

Optimizing MRI sequences and images for MRI-based stereotactic radiosurgery treatment planning

AimDevelopment of MRI sequences and processing methods for the production of images appropriate for direct use in stereotactic radiosurgery (SRS) treatment planning.BackgroundMRI is useful in SRS treatment planning, especially for patients with brain lesions or anatomical targets that are poorly distinguished by CT, but its use requires further refinement. This methodology seeks to optimize MRI sequences to generate distortion-free and clinically relevant MR images for MRI-only SRS treatment planning.Materials and methodsWe used commercially available SRS MRI-guided radiotherapy phantoms and eight patients to optimize sequences for patient imaging. Workflow involved the choice of correct MRI sequence(s), optimization of the sequence parameters, evaluation of image quality (artifact free and clinically relevant), measurement of geometrical distortion, and evaluation of the accuracy of our offline correction algorithm.ResultsCT images showed a maximum deviation of 1.3 mm and minimum deviation of 0.4 mm from true fiducial position for SRS coordinate definition. Interestingly, uncorrected MR images showed maximum deviation of 1.2 mm and minimum of 0.4 mm, comparable to CT images used for SRS coordinate definition. After geometrical correction, we observed a maximum deviation of 1.1 mm and minimum deviation of only 0.3 mm.ConclusionOur optimized MRI pulse sequences and image correction technique show promising results; MR images produced under these conditions are appropriate for direct use in SRS treatment planning.     

Nutrient limitations in wet, drained and rewetted fen meadows: evaluation of methods and results

Restoration of wet grassland communities on peat soils involves management of nutrient supply and hydrology. The concept of nutrient limitation was discussed as well as its interaction with drainage and rewetting of severely drained peat soils. Different methods of assessing nutrient limitation were compared and the type and extent of nutrient limitation were determined for several wet grassland communities. It was concluded that a full-factorial field fertilisation experiment is the most preferable method. Plant tissue analyses and soil chemical analyses were considered less suitable, although they may provide helpful additional information. Fertilisation experiments in the laboratory using sods or using test plants appear to be the proper means to study mechanisms or processes, but have a restricted predictive value for field situations. Generalising the results, it seems that many relativily undisturbed grassland plant communities on peaty soils are characterised by N limitation. Phosphate limitation for vegetation on peat soils is mainly observed in specific circumstances such as extreme calcium richness, high concentrations of Fe or as a result of drainage or long-term hay cropping. The latter two may also cause K limitation. Rewetting is regarded as a prerequisite in restoring wet grassland communities. Further restoration measures to influence nutrient availability depend on aims of the management and the individual site conditions. This revised version was published online in June 2006 with corrections to the Cover Date.     

Dosimetric comparison between two MLC systems commonly used for stereotactic radiosurgery and radiotherapy: A Monte Carlo and experimental study

In this work dosimetric parameters of two multi-leaf collimator (MLC) systems, namely the beam modulator (BM), which is the MLC commercial name for Elekta “Synergy S” linear accelerator and Radionics micro-MLC (MMLC), are compared using measurements and Monte Carlo simulations. Dosimetric parameters, such as percentage depth doses (PDDs), in-plane and cross-plane dose profiles, and penumbras for different depths and field sizes of the 6 MV photon beams were measured using ionization chamber and a water tank. The collimator leakages were measured using radiographic films. MMLC and BM were modeled using the EGSnrc-based BEAMnrc Monte Carlo code and above dosimetric parameters were calculated. The energy fluence spectra for the two MLCs were also determined using the BEAMnrc and BEAMDP. Dosimetric parameters of the two MLCs were similar, except for penumbras. Leaf-side and leaf-end 80–20% dose penumbras at 10 cm depth for a 10 × 10 cm² field size were 4.8 and 5.1 mm for MMLC and 5.3 mm and 6.3 mm for BM, respectively. Both Radionics MMLC and Elekta BM can be used effectively based on their dosimetric characteristics for stereotactic radiosurgery and radiotherapy, although the former showed slightly sharper dose penumbra especially in the leaf-end direction.     

Biological dosimetry intercomparison exercise: an evaluation of triage and routine mode results by robust methods

Well-defined protocols and quality management standards are indispensable for biological dosimetry laboratories. Participation in periodic proficiency testing by interlaboratory comparisons is also required. This harmonization is essential if a cooperative network is used to respond to a mass casualty event. Here we present an international intercomparison based on dicentric chromosome analysis for dose assessment performed in the framework of the IAEA Regional Latin American RLA/9/054 Project. The exercise involved 14 laboratories, 8 from Latin America and 6 from Europe. The performance of each laboratory and the reproducibility of the exercise were evaluated using robust methods described in ISO standards. The study was based on the analysis of slides from samples irradiated with 0.75 (DI) and 2.5 Gy (DII). Laboratories were required to score the frequency of dicentrics and convert them to estimated doses, using their own dose-effect curves, after the analysis of 50 or 100 cells (triage mode) and after conventional scoring of 500 cells or 100 dicentrics. In the conntional scoring, at both doses, all reported frequencies were considered as satisfactory, and two reported doses were considered as questionable. The analysis of the data dispersion among the dicentric frequencies and among doses indicated a better reproducibility for estimated doses (15.6% for DI and 8.8% for DII) than for frequencies (24.4% for DI and 11.4% for DII), expressed by the coefficient of variation. In the two triage modes, although robust analysis classified some reported frequencies or doses as unsatisfactory or questionable, all estimated doses were in agreement with the accepted error of ±0.5 Gy. However, at the DI dose and for 50 scored cells, 5 out of the 14 reported confidence intervals that included zero dose and could be interpreted as false negatives. This improved with 100 cells, where only one confidence interval included zero dose. At the DII dose, all estimations fell within ±0.5 Gy of the reference dose interval. The results obtained in this triage exercise indicated that it is better to report doses than frequencies. Overall, in both triage and conventional scoring modes, the laboratory performances were satisfactory for mutual cooperation purposes. These data reinforce the view that collaborative networking in the case of a mass casualty event can be successful.     

Stress echocardiography: methods,indications and results

Stress echocardiography has become an important clinical tool to detect cardiac ischaemia and viability in addition to single photon emission tomography. Stress echocardiography has a high positive and negative predictive value, is less expensive than the nuclear methods and has no radiation exposure. It can easily be used in an emergency room and coronary care unit. Because of its feasibility, low cost and high diagnostic accuracy, it will become a very important technique in every hospital and will soon be a real alternative to the more time-consuming and expensive nuclear techniques. The current article gives a review of the methods of stress echocardiography.     

Spot-scanned pancreatic stereotactic body proton therapy: A dosimetric feasibility and robustness study

PurposeWe explored the dosimetric potential of spot-scanned stereotactic body proton therapy (SBPT) for pancreatic cancer.MethodsWe compared SBPT to stereotactic body intensity-modulated radiotherapy (SB-IMRT) in 10 patients. We evaluated 3 variables in SBPT planning: (1) 4 and 6 mm spot size; (2) single vs. multi-field optimization (SFO vs. MFO); and (3) optimization target volume (OTV) expansion. Robustness analysis was performed with unidirectional isocenter shifts of ±3 mm in x, y, and z and ±3% stopping power uncertainties.ResultsSBPT plans had lower V_10Gy for the stomach and small and large bowels. Under static robustness, a 5 mm OTV and SFO-6 mm spot size represented the best compromise between target and normal structure. A 4-mm spot-size and 3 mm OTV resulted in significant target underdosing with deformable dose accumulation analysis.ConclusionsThis study provides a critical basis for clinical translation of spot size, optimization technique, and OTV expansion for pancreatic SBPT.     

Differential diagnosis between progression and radionecrosis in brain metastases after stereotactic radiosurgery using hybrid FDG-PET and MRI coregistered images

IntroductionDual phase 18 FDG brain PET is helpful to assess brain metastases (BM) as tracer will build up in metastases or tumor recurrences while its retention remains stable within normal tissue or inflammatory processes. This is useful when MRI can’t discriminate brain tumor recurrence (TR) rom radionecrosis (RN) after stereotaxic radiosurgery (SRS) for BM. Many studies have sought to improve diagnostic performance by associating FDG-PET and MRI with interesting results but many biases, mostly within image post-processing. Coregistered MRI and dual phase FDG-PET images could alleviate these biases and be used to extract prognostic biomarkers.Materials and methodsWe retrospectively evaluated patients treated with SRS for BM which developed a contrast-enhanced MRI lesion with non-conclusive diagnosis for TR or RN. All patients underwent MRI and FDG-PET at least 3 months after their last SRS session. Dual FDG-PET consisted in an “early” and “delayed” acquisition, respectively 30 minutes and 4 h after injection. MRI included permeability and perfusion sequences. PET and MRI data were all coregistered on the contrast enhanced T1 MRI images. Semi-automated Volumes of Interest (VOI) of the tumor were drawn on the BM and a reference contralateral white-matter ROI (WM) was drawn for standardization; every metric was calculated inside these ROIs, in particular the tumor SUVmax and its variation in time. A 20% increase in the tumor SUVmax was in favor of TR while a modification of less than 100% was in favor of RN. Imaging metrics were then evaluated for their association with TR or RN based on histological, radiological and clinical criteria after at least 6 months follow-up.ResultsNine patients were ruled out as TR and 6 as RN. After standardization, there was a significant difference between groups for VP (P = 0.042), Washin (P = 0.035), Peak Enhancement (P = 0.037), standardized delayed SUVmax (P = 0.008) and RI (P = 0.016). Semi-quantitative analysis found respectively for PET and MRI a Sensitivity of 100% and 87.5% and a Specificity of 100% and 85.71%.ConclusionCoregistered PET-MRI images accurately discriminate between TR and RN. With FDG being the most commonly used PET radiotracer, this protocol remains easily transposable and should be encouraged to obtain non-invasive prognostic and clinically relevant biomarkers.     

Geometric inaccuracy and co-registration errors for CT,DynaCT and MRI images used in robotic stereotactic radiosurgery treatment planning

PurposeTo measure the combined errors due to geometric inaccuracy and image co-registration on secondary images (dynamic CT angiography (dCTA), 3D DynaCT angiography (DynaCTA), and magnetic resonance images (MRI)) that are routinely used to aid in target delineation and planning for stereotactic radiosurgery (SRS).MethodsThree phantoms (one commercial and two in-house built) and two different analysis approaches (commercial and MATLAB based) were used to quantify the magnitude of geometric image distortion and co-registration errors for different imaging modalities within CyberKnife’s MultiPlan treatment planning software. For each phantom, the combined errors were reported as a mean target registration error (TRE). The mean TRE’s for different intramodality imaging parameters (e.g., mAs, kVp, and phantom set-ups) and for dCTA, DynaCTA, and MRI systems were measured.ResultsOnly X-ray based imaging can be performed with the commercial phantom, and the mean TRE ± standard deviation values were large compared to the in-house analysis using MATLAB. With the 3D printed phantom, even drastic changes in treatment planning CT imaging protocols did not greatly influence the mean TRE (<0.5 mm for a 1 mm slice thickness CT). For all imaging modalities, the largest mean TRE was found on DynaCT, followed by T2-weighted MR images (albeit all <1 mm).ConclusionsThe user may overestimate the mean TRE if the commercial phantom and MultiPlan were used solely. The 3D printed phantom design is a sensitive and suitable quality assurance tool for measuring 3D geometric inaccuracy and co-registration errors across all imaging modalities.     

Assessment of mite numbers: New methods and results

The determination of mite numbers in dust samples depends on the effectiveness of the sampling procedure. We report on mite isolation from dust samples by flotation distinguishing between living and dead mites. The results are varied and unreproducible; ageing processes are of relevance in the case of dead mites. Living mites can be determined more reliably when using mite mobility. Two methods based on this principle, the mobility test and the heat escape method, are described and discussed. In the case of a natural analogous mite development on carpets, mite numbers ranging from 80 000 to 200 000 mites per m² are found after approx. 3 months. It is shown that the mobility of different mite species varies. The mobility test allows the detection of mites in textile objects, and shows how mites are distributed over these objects. It is demonstrated how the infestation of clothes by mites can be determined.     

Setup uncertainties in linear accelerator based stereotactic radiosurgery and a derivation of the corresponding setup margin for treatment planning

PurposeIn the present study, clinical stereotactic radiosurgery (SRS) setup uncertainties from image-guidance data are analyzed, and the corresponding setup margin is estimated for treatment planning purposes.MethodsPatients undergoing single-fraction SRS at our institution were localized using invasive head ring or non-invasive thermoplastic masks. Setup discrepancies were obtained from an in-room x-ray patient position monitoring system. Post treatment re-planning using the measured setup errors was performed in order to estimate the individual target margins sufficient to compensate for the actual setup errors. The formula of setup margin for a general SRS patient population was derived by proposing a correlation between the three-dimensional setup error and the required minimal margin.ResultsSetup errors of 104 brain lesions were analyzed, in which 81 lesions were treated using an invasive head ring, and 23 were treated using non-invasive masks. In the mask cases with image guidance, the translational setup uncertainties achieved the same level as those in the head ring cases. Re-planning results showed that the margins for individual patients could be smaller than the clinical three-dimensional setup errors. The derivation of setup margin adequate to address the patient setup errors was demonstrated by using the arbitrary planning goal of treating 95% of the lesions with sufficient doses.ConclusionsWith image guidance, the patient setup accuracy of mask cases can be comparable to that of invasive head rings. The SRS setup margin can be derived for a patient population with the proposed margin formula to compensate for the institution-specific setup errors.     

Comparison of (125)I stereotactic brachytherapy and LINAC radiosurgery modalities based on physical dose distribution and radiobiological efficacy

The goal of this study was to make a comparison between stereotactic brachytherapy implants and linear accelerator-based radiosurgery of brain tumors with respect to physical dose distributions and radiobiological efficacy. Twenty-four treatment plans made for irradiation of brain tumors with low-dose-rate (125)I brachytherapy and multiple-arc LINAC-based radiosurgery were analyzed. Using the dose-volume histograms and the linear-quadratic model, the brachytherapy doses were compared to the brachytherapy-equivalent LINAC radiosurgery doses with respect to the predicted late effects of radiation on normal brain tissue. To characterize the conformity and homogeneity of dose distributions, the conformal index, external volume index, and relative homogeneity index were calculated for each dose plan and the mean values were compared. The average tumor volume was 5.6 cm(3) (range: 0.1-19.3 cm(3)). At low doses, the calculated radiobiological late effect on normal tissue was equivalent for external-beam and brachytherapy dose delivery. For brachytherapy at doses greater than 30 Gy, the calculated equivalent dose to normal tissues was less than for external-beam radiosurgery. However, the dose-calculated homogeneity was better for the LINAC radiosurgery, with a mean relative homogeneity index of 0.62 compared to the calculated value of 0.19 for the brachytherapy (P=0.0002). These results are only predictions based on calculations concerning normal tissue tolerance. More data and research are needed to understand the clinical relevance of these findings.     

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.