Dosimetric and NTCP advantages of robust proton therapy over robust VMAT for Stage III NSCLC in the immunotherapy era.

AIMS: To assess the robustness and to define the dosimetric and NTCP advantages of pencil-beam-scanning proton therapy (PBSPT) compared with VMAT for unresectable Stage III non-small lung cancer (NSCLC) in the immunotherapy era. MATERIAL AND METHODS: 10 patients were re-planned with VMAT and PBSPT using: 1) ITV-based robust optimization with 0.5 cm setup uncertainties and (for PBSPT) 3.5 % range uncertainties on free-breathing CT 2) CTV-based RO including all 4DCTs anatomies. Target coverage (TC), organs at risk dose and TC robustness (TCR), set at V95%, were compared. The NTCP risk for radiation pneumonitis (RP), 24-month mortality (24MM), G2 + acute esophageal toxicity (ET), the dose to the immune system (EDIC) and the left anterior descending (LAD) coronary artery V15 < 10 % were registered. Wilcoxon test was used. RESULTS: Both PBSPT methods improved TC and TCR (p < 0.01). The mean lung dose and lung V20 were lower with PBSPT (p < 0.01). Median mean heart dose reduction with PBSPT was 8 Gy (p < 0.001). PT lowered median LAD V15 (p = 0.004). ΔNTCP > 5 % with PBSPT was observed for two patients for RP and for five patients for 24 MM. ΔNTCP for ≥ G2 ET was not in favor of PBSPT for all patients. PBSPT halved median EDIC (4.9/5.1 Gy for ITV/CTV-based VMAT vs 2.3 Gy for both ITV/CTV-based PBSPT, p < 0.01). CONCLUSIONS: PBSPT is a robust approach with significant dosimetric and NTCP advantages over VMAT; the EDIC reduction could allow for a better integration with immunotherapy. A clinical benefit for a subset of NSCLC patients is expected.

Characterisation of grids of point detectors in maximum skin dose measurement in fluoroscopically-guided interventional procedures.

PURPOSE: Point detectors are frequently used to measure patient's maximum skin dose (MSD) in fluoroscopically-guided interventional procedures (IP). However, their performance and ability to detect the actual MSD are rarely evaluated. The present study investigates the sampling uncertainty associated with the use of grids of point detectors to measure MSD in IP. METHOD: Chemoembolisation of the liver (CE), percutaneous coronary intervention (PCI) and neuroembolisation (NE) procedures were studied. Spatial dose distributions were measured with XR-RV3 Gafchromic(®) films for 176 procedures. These distributions were used to simulate measurements performed using grids of detectors such as thermoluminescence detectors, with detector spacing from 1.4 up to 10 cm. RESULTS: The sampling uncertainty was the highest in PCI and NE procedures. With 40 detectors covering the film area (36 cm × 44 cm), the maximum dose would be on average 86% and 63% of the MSD measured with Gafchromic(®) films in CE and PCI procedures, respectively. In NE procedures, with 27 detectors covering the film area (14 cm × 35 cm), the maximum dose measured would be on average 82% of the MSD obtained with the Gafchromic(®) films. CONCLUSION: Thermoluminescence detectors show good energy and dose response in clinical beam qualities. However the poor spatial resolution of such point-like dosimeters may far outweigh their good dosimetric properties. The uncertainty from the sampling procedure should be estimated when point detectors are used in IP because it may lead to strong underestimation of the MSD.

Characterization of XR-RV3 GafChromic(®) films in standard laboratory and in clinical conditions and means to evaluate uncertainties and reduce errors.

PURPOSE: To investigate the optimal use of XR-RV3 GafChromic(®) films to assess patient skin dose in interventional radiology while addressing the means to reduce uncertainties in dose assessment. METHODS: XR-Type R GafChromic films have been shown to represent the most efficient and suitable solution to determine patient skin dose in interventional procedures. As film dosimetry can be associated with high uncertainty, this paper presents the EURADOS WG 12 initiative to carry out a comprehensive study of film characteristics with a multisite approach. The considered sources of uncertainties include scanner, film, and fitting-related errors. The work focused on studying film behavior with clinical high-dose-rate pulsed beams (previously unavailable in the literature) together with reference standard laboratory beams. RESULTS: First, the performance analysis of six different scanner models has shown that scan uniformity perpendicular to the lamp motion axis and that long term stability are the main sources of scanner-related uncertainties. These could induce errors of up to 7% on the film readings unless regularly checked and corrected. Typically, scan uniformity correction matrices and reading normalization to the scanner-specific and daily background reading should be done. In addition, the analysis on multiple film batches has shown that XR-RV3 films have generally good uniformity within one batch (<1.5%), require 24 h to stabilize after the irradiation and their response is roughly independent of dose rate (<5%). However, XR-RV3 films showed large variations (up to 15%) with radiation quality both in standard laboratory and in clinical conditions. As such, and prior to conducting patient skin dose measurements, it is mandatory to choose the appropriate calibration beam quality depending on the characteristics of the x-ray systems that will be used clinically. In addition, yellow side film irradiations should be preferentially used since they showed a lower dependence on beam parameters compared to white side film irradiations. Finally, among the six different fit equations tested in this work, typically used third order polynomials and more rational and simplistic equations, of the form dose inversely proportional to pixel value, were both found to provide satisfactory results. Fitting-related uncertainty was clearly identified as a major contributor to the overall film dosimetry uncertainty with up to 40% error on the dose estimate. CONCLUSIONS: The overall uncertainty associated with the use of XR-RV3 films to determine skin dose in the interventional environment can realistically be estimated to be around 20% (k = 1). This uncertainty can be reduced to within 5% if carefully monitoring scanner, film, and fitting-related errors or it can easily increase to over 40% if minimal care is not taken. This work demonstrates the importance of appropriate calibration, reading, fitting, and other film-related and scan-related processes, which will help improve the accuracy of skin dose measurements in interventional procedures.

Measurement of maximum skin dose in interventional radiology and cardiology and challenges in the set-up of European alert thresholds.

To help operators acknowledge patient dose during interventional procedures, EURADOS WG-12 focused on measuring patient skin dose using XR-RV3 gafchromic films, thermoluminescent detector (TLD) pellets or 2D TL foils and on investigating possible correlation to the on-line dose indicators such as fluoroscopy time, Kerma-area product (KAP) and cumulative air Kerma at reference point (CK). The study aims at defining non-centre-specific European alert thresholds for skin dose in three interventional procedures: chemoembolization of the liver (CE), neuroembolization (NE) and percutaneous coronary interventions (PCI). Skin dose values of >3 Gy (ICRP threshold for skin injuries) were indeed measured in these procedures confirming the need for dose indicators that correlate with maximum skin dose (MSD). However, although MSD showed fairly good correlation with KAP and CK, several limitations were identified challenging the set-up of non-centre-specific European alert thresholds. This paper presents preliminary results of this wide European measurement campaign and focuses on the main challenges in the definition of European alert thresholds.

Reference levels at European level for cardiac interventional procedures.

In interventional cardiology, a wide variation in patient dose for the same type of procedure has been recognised by different studies. Variation is almost due to procedure complexity, equipment performance, procedure protocol and operator skill. The SENTINEL consortium has performed a survey in nine european centres collecting information on near 2000 procedures, and a new set of reference levels (RLs) for coronary angiography and angioplasty and diagnostic electrophysiology has been assessed for air kerma-area product: 45, 85 and 35 Gy cm2, effective dose: 8, 15 and 6 mSv, cumulative dose at interventional reference point: 650 and 1500 mGy, fluoroscopy time: 6.5, 15.5 and 21 min and cine frames: 700 and 1000 images, respectively. Because equipment performance and set-up are the factors contributing to patient dose variability, entrance surface air kerma for fluoroscopy, 13 mGy min(-1), and image acquisition, 0.10 mGy per frame, have also been proposed in the set of RLs.

Survey on performance assessment of cardiac angiography systems.

Advances in imaging technology have facilitated the development of increasingly complex interventional cardiac equipment. Consequently, there is a need for definitive equipment requirements. The aim of the study is to assess the performances of different cardiac angiographic systems. A questionnaire was sent to centres participating in SENTINEL Project to collect dosimetry data (typical entrance dose rate in fluoroscopy and imaging mode), image quality evaluations (low and high contrast resolutions) and KAP calibration factors. Results from this survey could contribute to the explanation of patient dose variability in angiographic cardiac procedures and to derive reference levels for cardiac angiographic equipment performance parameters.

Quality criteria for cardiac images: an update.

The DIMOND II and III Cardiology Groups have agreed on quality criteria for cardiac images and developed a scoring system, to provide a tool to test quality of coronary angiograms, which was demonstrated to be of value in clinical practice. In the last years, digital flat panel technology has been introduced in cardiac angiographic systems and the radiological technique may have been influenced by the better performance of these new detectors. This advance in digital imaging, together with the lesson learned from previous studies, warranted the revision of the quality criteria for cardiac angiographic images as formerly defined. DIMOND criteria were reassessed to allow a simpler evaluation of angiograms. Clinical criteria were simplified and separated from technical criteria. Furthermore, the characteristics of an optimised angiographic technique have been outlined.

Staff dosimetry in interventional cardiology: survey on methods and level of exposure.

In interventional cardiac procedures, staff operates near the patient in a non-uniformly scattered radiation field. Consequently, workers may receive, over a period, relatively high radiation doses. The measurement of individual doses to personnel becomes critical due to the use of protective devices and, as a consequence of the large number of methods proposed to assess the effective dose, great variability in monitoring programmes is expected among European countries. SENTINEL consortium has conducted a survey on staff dosimetry methods and on the level of staff exposure in 12 European cardiac centres demonstrating the urgent need to harmonise dosimetry methods. From the dosimetry survey, constraint annual effective dose of 1.4 mSv and Hp(0.07) over the protective apron of 14 mSv are proposed for the optimisation the exposure the most-exposed operator.

The possible role of chromogranin A as a prognostic factor in organ-confined prostate cancer.

The clinical significance of neuroendocrine differentiation in patients who have undergone surgery for localized prostate cancer is still unclear. The aims of this study were to assess the relationship between serum neuroendocrine markers and well-known prognostic factors in prostate cancer (pathological staging, definitive Gleason score and serum PSA) and to search for correlations between serum chromogranin A (CgA) levels and pathological findings. Forty-one consecutive patients who had undergone radical retropubic prostatectomy for clinically localized prostate cancer were evaluated. Serum PSA, CgA and neuron-specific enolase were measured immediately before surgery. Twenty-six surgical specimens were phenotypically and immunohistochemically evaluated using an antibody against CgA. Significant correlations were found between serum CgA, pathological staging and Gleason score (p=0.049 and p=0.038, respectively). Serum CgA did not correlate with PSA, patient age, or immunohistochemical findings. There was a significant correlation between positive immunohistochemical CgA staining and Gleason score (p=0.014). An increase in serum CgA levels, independent of PSA values, might be the expression of pathologically more advanced tumor stage and higher Gleason score; this could help to identify a high-risk patient group eligible for adjuvant therapy.

Dose to cardiologists in haemodynamic and electrophysiology cardiac interventional procedures.

Interventional cardiac procedures can be complex and involve extensive use of low dose rate fluoroscopy and high dose rate in image acquisition mode; hence, staff may receive significant radiation exposure. Radiation exposure to operators was assessed in 173 procedures. Fluoroscopy time, number of acquired images and dose-area product were recorded and occupational dose assessed with thermoluminescence dosemeters. The effective dose to the operator was compared with relevant literature data: values found were generally lower than those reported for other interventional cardiology laboratories. This is probably because of the strict radiation protection policy in our centre. Higher effective doses were found for defibrillator implantation and percutaneous transluminal coronary angiography procedures; for other cardiac procedures, effective dose was lower. Yearly extrapolated occupational doses to cardiologists are lower than the regulatory dose limit and in the lower band of doses reported in the literature.

Patient skin dosimetry in haemodynamic and electrophysiology interventional cardiology.

With the increase in number and complexity of interventional cardiology (IC) procedures, it is important to monitor skin dose in order to decrease skin injuries. This study investigated radiation doses for patients undergoing IC procedures, compare results with the literature and define a local dose-area product trigger level for operators to identify situations likely to exceed the threshold for transient skin erythema of 2 Gy. Dosimetric data were collected for 77 haemodynamic and 90 electrophysiological procedures. Mean maximum local skin doses (MSDs) were 0.28 Gy for coronary angiography, 1.03 Gy for percutaneous transluminal coronary angioplasty (PTCA), 0.03 Gy for pacemaker insertion, 0.17 Gy for radiofrequency ablation for nodal tachycardia, 0.10 Gy for WPW and 0.22 Gy for atrial flutter. Since MSD values for the other procedures were well below the deterministic effect limit, a trigger level of 140 Gy cm2 was derived for PTCA procedures alone.

Are new technologies always reducing patient doses in cardiac procedures?

Dynamic digital flat-panel (FD) imaging technology is characterised by a higher sensitivity and image quality compared to image intensifier (II) technology. In this study, an angiography system based on II and one based on FD were compared with respect to system performance and impact of patient dose in interventional cardiology. When entrance surface air kerma rates are measured, the FD system requires a reduced dose rate, of up to 40%. For coronary angiography (CA), fluoroscopy time (FT) and dose-area product (DAP) were 4.3 +/- 5.0 min and 31.2 +/- 30.2 Gy cm2 on the II system and 4.4 +/- 3.8 min and 33.4 +/- 19.2 Gy cm2 with the FD system. For percutaneous transluminal coronary angiography, FT and DAP were 11.4 +/- 10.7 min and 52.1 +/- 45.0 Gy cm2 on II and 10.7 +/- 8.7 min and 66.9 +/- 54.4 Gy cm2 on DF. Data comparison suggests that reduced entrance dose rates do not automatically imply a reduction of patient dose in clinical practice.