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.

Robustness evaluation of pencil beam scanning proton therapy treatment planning: A systematic review.

Compared to conventional radiotherapy using X-rays, proton therapy, in principle, allows better conformity of the dose distribution to target volumes, at the cost of greater sensitivity to physical, anatomical, and positioning uncertainties. Robust planning, both in terms of plan optimization and evaluation, has gained high visibility in publications on the subject and is part of clinical practice in many centers. However, there is currently no consensus on the methods and parameters to be used for robust optimization or robustness evaluation. We propose to overcome this deficiency by following the modified Delphi consensus method. This method first requires a systematic review of the literature. We performed this review using the PubMed and Web Of Science databases, via two different experts. Potential conflicts were resolved by a third expert. We then explored the different methods before focusing on clinical studies that evaluate robustness on a significant number of patients. Many robustness assessment methods are proposed in the literature. Some are more successful than others and their implementation varies between centers. Moreover, they are not all statistically or mathematically equivalent. The most sophisticated and rigorous methods have seen more limited application due to the difficulty of their implementation and their lack of widespread availability.

ESTRO-ACROP guideline on surface guided radiation therapy.

Surface guidance systems enable patient positioning and motion monitoring without using ionising radiation. Surface Guided Radiation Therapy (SGRT) has therefore been widely adopted in radiation therapy in recent years, but guidelines on workflows and specific quality assurance (QA) are lacking. This ESTRO-ACROP guideline aims to give recommendations concerning SGRT roles and responsibilities and highlights common challenges and potential errors. Comprehensive guidelines for procurement, acceptance, commissioning, and QA of SGRT systems installed on computed tomography (CT) simulators, C-arm linacs, closed-bore linacs, and particle therapy treatment systems are presented that will help move to a consensus among SGRT users and facilitate a safe and efficient implementation and clinical application of SGRT.

Evaluation of the water-equivalence of plastic materials in low- and high-energy clinical proton beams.

The aim of this work was to evaluate the water-equivalence of new trial plastics designed specifically for light-ion beam dosimetry as well as commercially available plastics in clinical proton beams. The water-equivalence of materials was tested by computing a plastic-to-water conversion factor, [Formula: see text]. Trial materials were characterized experimentally in 60 MeV and 226 MeV un-modulated proton beams and the results were compared with Monte Carlo simulations using the FLUKA code. For the high-energy beam, a comparison between the trial plastics and various commercial plastics was also performed using FLUKA and Geant4 Monte Carlo codes. Experimental information was obtained from laterally integrated depth-dose ionization chamber measurements in water, with and without plastic slabs with variable thicknesses in front of the water phantom. Fluence correction factors, [Formula: see text], between water and various materials were also derived using the Monte Carlo method. For the 60 MeV proton beam, [Formula: see text] and [Formula: see text] factors were within 1% from unity for all trial plastics. For the 226 MeV proton beam, experimental [Formula: see text] values deviated from unity by a maximum of about 1% for the three trial plastics and experimental results showed no advantage regarding which of the plastics was the most equivalent to water. Different magnitudes of corrections were found between Geant4 and FLUKA for the various materials due mainly to the use of different nonelastic nuclear data. Nevertheless, for the 226 MeV proton beam, [Formula: see text] correction factors were within 2% from unity for all the materials. Considering the results from the two Monte Carlo codes, PMMA and trial plastic #3 had the smallest [Formula: see text] values, where maximum deviations from unity were 1%, however, PMMA range differed by 16% from that of water. Overall, [Formula: see text] factors were deviating more from unity than [Formula: see text] factors and could amount to a few percent for some materials.

Investigation into the effects of high-Z nano materials in proton therapy.

High-Z nano materials have been previously shown to increase the amount of dose deposition within the tumour due to an increase in secondary electrons. This study evaluates the effects of high-Z nano materials in combination with protons, and the impact of proton energy, nanoparticle material and concentration. These effects were studied in silico through Monte Carlo simulation and experimentally through a phantom study, with particular attention to macroscale changes to the Bragg peak in the presence of nanoparticles. Three nanoparticle materials were simulated (gold, silver and platinum) at three concentrations (0.01, 0.1 and 6.5 mg ml(-1)) at two clinical proton energies (60 and 226 MeV). Simulations were verified experimentally using Gafchromic film measurements of gold nanoparticles suspended in water at two available high concentrations (5.5 mg ml(-1) and 1.1 mg ml(-1)). A significant change to Bragg peak features was evident, where at 226 MeV and 6.5 mg ml(-1), simulations of gold showed a 4.7 mm longitudinal shift of the distal edge and experimentally at 5.5 mg ml(-1), a shift of 2.2 mm. Simulations showed this effect to be material dependent, where platinum having the highest physical density caused the greatest shift with increasing concentration. A dose enhancement of 6% ± 0.05 and 5% ± 0.15 (60 MeV and 226 MeV, respectively) was evident with gold at 6.5 mg ml(-1) to water alone, compared to the 21% ± 0.53 observed experimentally as dose to film with 5.5 mg ml(-1) of gold nanoparticles suspended in water at 226 MeV. The introduction of nanoparticles has strong potential to enhance dose in proton therapy, however the changes to the Bragg peak distribution that occur with high concentrations need to be accounted for to ensure tumour coverage.

Characterization and validation of a Monte Carlo code for independent dose calculation in proton therapy treatments with pencil beam scanning.

We propose a method of creating and validating a Monte Carlo (MC) model of a proton Pencil Beam Scanning (PBS) machine using only commissioning measurements and avoiding the nozzle modeling. Measurements with a scintillating screen coupled with a CCD camera, ionization chamber and a Faraday Cup were used to model the beam in TOPAS without using any machine parameter information but the virtual source distance from the isocenter. Then the model was validated on simple Spread Out Bragg Peaks (SOBP) delivered in water phantom and with six realistic clinical plans (many involving 3 or more fields) on an anthropomorphic phantom. In particular the behavior of the moveable Range Shifter (RS) feature was investigated and its modeling has been proposed. The gamma analysis (3%,3 mm) was used to compare MC, TPS (XiO-ELEKTA) and measured 2D dose distributions (using radiochromic film). The MC modeling proposed here shows good results in the validation phase, both for simple irradiation geometry (SOBP in water) and for modulated treatment fields (on anthropomorphic phantoms). In particular head lesions were investigated and both MC and TPS data were compared with measurements. Treatment plans with no RS always showed a very good agreement with both of them (γ-Passing Rate (PR) > 95%). Treatment plans in which the RS was needed were also tested and validated. For these treatment plans MC results showed better agreement with measurements (γ-PR > 93%) than the one coming from TPS (γ-PR < 88%). This work shows how to simplify the MC modeling of a PBS machine for proton therapy treatments without accounting for any hardware components and proposes a more reliable RS modeling than the one implemented in our TPS. The validation process has shown how this code is a valid candidate for a completely independent treatment plan dose calculation algorithm. This makes the code an important future tool for the patient specific QA verification process.

[Allergic diseases caused by pesticides: 3 case reports]. / Allergopatie da pesticidi: descrizione di tre casi.

Current pesticide exposure levels can induce a state of sensitization in exposed workers and only in exceptional situations cause severe intoxication. Three cases are reported--one suffering from urticaria/angio-edema, one from asthma and the other from oculo-rhinitis. Only one subject was atopical. The substances to which sensitization was found were Cynoxamil, Mancozeb, Thiophanate, Seccatutto for the first case, Paraquat for the second and Dodine for the third subject. The results suggest the need to extend allergological tests also to pesticides when workers, or subjects in any case exposed, show clinical signs with suspected immunological pathogenesis. Furthermore, in order to reduce the number of new cases of pesticide allergy, a more severe control also of subjects exposed to low doses is proposed.