S. Lorentini

Intensity-modulated radiation therapy in newly diagnosed glioblastoma: a systematic review on clinical and technical issues.

BACKGROUND AND PURPOSE Intensity-modulated radiation therapy (IMRT) could represent a new tool to improve the therapeutic ratio in the treatment of glioblastoma. This systematic review investigates the evidence behind the application of IMRT to glioblastoma, assessing the potential benefits from both the clinical and dosimetrical perspective. MATERIALS AND METHODS Two independent researchers systematically identified all relevant articles available on PubMed and MEDLINE databases until December 2009. RESULTS Ultimately, seventeen studies were included in the analysis, for a total of 204 treated patients and 148 patient datasets used in planning studies. Most dosimetrical studies provided statistical analysis. Clinical series did not include any randomized controlled study, ultimately hindering a meta-analysis. From the dosimetrical point of view, conformal radiotherapy and IMRT provide similar results in terms of target coverage, while IMRT is better in terms of dose conformity, in reducing the maximum dose to the organs at risk and in healthy brain sparing. In clinical reports, a wide variability was recorded concerning dose per fraction, total dose, and chemotherapy administration. A comprehensive qualitative comparison with literature on similar non-IMRT clinical series showed that in most IMRT series excellent compliance and low rates of toxicity were recorded. Hypofractionated regimens in association with chemotherapy showed results that are even superior to the standard treatment. CONCLUSIONS According to the available data, the dosimetrical advantages of IMRT translate into the clinical capability of delivering higher dose levels in a shorter time. This approach in glioblastoma patients with good prognosis suggests the possibility of improving outcomes without an increase in toxicity.

Application of failure mode and effects analysis to treatment planning in scanned proton beam radiotherapy

BackgroundA multidisciplinary and multi-institutional working group applied the Failure Mode and Effects Analysis (FMEA) approach to the actively scanned proton beam radiotherapy process implemented at CNAO (Centro Nazionale di Adroterapia Oncologica), aiming at preventing accidental exposures to the patient.MethodsFMEA was applied to the treatment planning stage and consisted of three steps: i) identification of the involved sub-processes; ii) identification and ranking of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system, iii) identification of additional safety measures to be proposed for process quality and safety improvement. RPN upper threshold for little concern of risk was set at 125.ResultsThirty-four sub-processes were identified, twenty-two of them were judged to be potentially prone to one or more failure modes. A total of forty-four failure modes were recognized, 52% of them characterized by an RPN score equal to 80 or higher. The threshold of 125 for RPN was exceeded in five cases only. The most critical sub-process appeared related to the delineation and correction of artefacts in planning CT data. Failures associated to that sub-process were inaccurate delineation of the artefacts and incorrect proton stopping power assignment to body regions. Other significant failure modes consisted of an outdated representation of the patient anatomy, an improper selection of beam direction and of the physical beam model or dose calculation grid. The main effects of these failures were represented by wrong dose distribution (i.e. deviating from the planned one) delivered to the patient. Additional strategies for risk mitigation, easily and immediately applicable, consisted of a systematic information collection about any known implanted prosthesis directly from each patient and enforcing a short interval time between CT scan and treatment start. Moreover, (i) the investigation of dedicated CT image reconstruction algorithms, (ii) further evaluation of treatment plan robustness and (iii) implementation of independent methods for dose calculation (such as Monte Carlo simulations) may represent novel solutions to increase patient safety.ConclusionsFMEA is a useful tool for prospective evaluation of patient safety in proton beam radiotherapy. The application of this method to the treatment planning stage lead to identify strategies for risk mitigation in addition to the safety measures already adopted in clinical practice.

Experimental verification of IMPT treatment plans in an anthropomorphic phantom in the presence of delivery uncertainties

Clinically relevant intensity modulated proton therapy (IMPT) treatment plans were measured in a newly developed anthropomorphic phantom (i) to assess plan accuracy in the presence of high heterogeneity and (ii) to measure plan robustness in the case of treatment uncertainties (range and spatial). The new phantom consists of five different tissue substitute materials simulating different tissue types and was cut into sagittal planes so as to facilitate the verification of co-planar proton fields. GafChromic films were positioned in the different planes of the phantom, and 3D-IMPT and distal edge tracking (DET) plans were delivered to a volume simulating a skull base chordoma. In addition, treatments planned on CTs of the phantom with HU units modified were delivered to simulate systematic range uncertainties (range-error treatments). Finally, plans were delivered with the phantom rotated to simulate spatial errors. Results show excellent agreement between the calculated and the measured dose distribution: >99% and 98% of points with a gamma value <1 (3%/3 mm) for the 3D-IMPT and the DET plan, respectively. For both range and spatial errors, the 3D-IMPT plan was more robust than the DET plan. Both plans were more robust to range than to the spatial uncertainties. Finally, for range error treatments, measured distributions were compared to a model for predicting delivery errors in the treatment planning system. Good agreement has been found between the model and the measurements for both types of IMPT plan.

Is there a role for proton therapy in the treatment of hepatocellular carcinoma? A systematic review

This paper aimed to review the literature concerning the use of proton therapy systematically in the treatment of hepatocellular carcinoma, focusing on clinical results and technical issues. The literature search was conducted according to a specific protocol in the Medline and Scopus databases by two independent researchers covering the period of 1990-2012. Both clinical and technical studies referring to a population of patients actually treated with protons were included. The PRISMA guidelines for reporting systematic reviews were followed. A final set of 16 studies from seven proton therapy institutions worldwide were selected from an initial dataset of 324 reports. Seven clinical studies, five reports on technical issues, three studies on treatment related toxicity and one paper reporting both clinical results and toxicity analysis were retrieved. Four studies were not published as full papers. Passive scattering was the most adopted delivery technique. More than 900 patients with heterogeneous stages of disease were treated with various fractionation schedules. Only one prospective full paper was found. Local control was approximately 80% at 3-5years, average overall survival at 5years was 32%, with data comparable to surgery in the most favorable groups. Toxicity was low (mainly gastrointestinal). Normal liver V0Gy<30%volume and V30Gy<18-25%volume were suggested as cut-off values for hepatic toxicity. The good clinical results of the selected papers are counterbalanced by a low level of evidence. However, the rationale to enroll patients in prospective studies appears to be strong.

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.

Supine craniospinal irradiation in pediatric patients by proton pencil beam scanning

BACKGROUND AND PURPOSE Proton therapy is the emerging treatment modality for craniospinal irradiation (CSI) in pediatric patients. Herein, special methods adopted for CSI at proton Therapy Center of Trento by pencil beam scanning (PBS) are comprehensively described. MATERIALS AND METHODS Twelve pediatric patients were treated by proton PBS using two/three isocenters. Special methods refer to: (i) patient positioning in supine position on immobilization devices crossed by the beams; (ii) planning field-junctions via the ancillary-beam technique; (iii) achieving lens-sparing by three-beams whole-brain-irradiation; (iv) applying a movable-snout and beam-splitting technique to reduce the lateral penumbra. Patient-specific quality assurance (QA) program was performed using two-dimensional ion chamber array and γ-analysis. Daily kilovoltage alignment was performed. RESULTS PBS allowed to obtain optimal target coverage (mean D98%>98%) with reduced dose to organs-at-risk. Lens sparing was obtained (mean D1∼730cGyE). Reducing lateral penumbra decreased the dose to the kidneys (mean Dmean<600cGyE). After kilovoltage alignment, potential dose deviations in the upper and lower junctions were small (average 0.8% and 1.2% respectively). Due to imperfect modeling of range shifter, QA showed better agreements between measurements and calculations at depths >4cm (mean γ>95%) than at depths<4cm. CONCLUSIONS The reported methods allowed to effectively perform proton PBS CSI.

Improvements in pencil beam scanning proton therapy dose calculation accuracy in brain tumor cases with a commercial Monte Carlo algorithm

A commercial Monte Carlo (MC) algorithm (RayStation version 6.0.024) for the treatment of brain tumors with pencil beam scanning (PBS) proton therapy is validated and compared via measurements and analytical calculations in clinically realistic scenarios. For the measurements a 2D ion chamber array detector (MatriXX PT) was placed underneath the following targets: (1) an anthropomorphic head phantom (with two different thicknesses) and (2) a biological sample (i.e. half a lambs head). In addition, we compared the MC dose engine versus the RayStation pencil beam (PB) algorithm clinically implemented so far, in critical conditions such as superficial targets (i.e. in need of a range shifter (RS)), different air gaps, and gantry angles to simulate both orthogonal and tangential beam arrangements. For every plan the PB and MC dose calculations were compared to measurements using a gamma analysis metrics (3%, 3 mm). For the head phantom the gamma passing rate (GPR) was always  >96% and on average  >99% for the MC algorithm; the PB algorithm had a GPR of  ⩽90% for all the delivery configurations with a single slab (apart 95% GPR from the gantry of 0° and small air gap) and in the case of two slabs of the head phantom the GPR was  >95% only in the case of small air gaps for all three (0°, 45°, and 70°) simulated beam gantry angles. Overall the PB algorithm tends to overestimate the dose to the target (up to 25%) and underestimate the dose to the organ at risk (up to 30%). We found similar results (but a bit worse for the PB algorithm) for the two targets of the lambs head where only two beam gantry angles were simulated. Our results suggest that in PBS proton therapy a range shifter (RS) needs to be used with caution when planning a treatment with an analytical algorithm due to potentially great discrepancies between the planned dose and the dose delivered to the patient, including in the case of brain tumors where this issue could be underestimated. Our results also suggest that a MC evaluation of the dose has to be performed every time the RS is used and, mostly, when it is used with large air gaps and beam directions tangential to the patient surface.

Clinical Pencil Beam Scanning: Present and Future Practices

Pencil beam scanning (PBS) is the most advanced beam delivery technology in particle therapy nowadays. After a pioneering phase, PBS is rapidly becoming available on a larger scale worlwide, and is expected to be the standard beam delivery technique in the future to come. The characterization of a PBS isocentric gantry involves a number of validation tests both at the hardware level (e.g. mechanical isocentricity of gantry and patient positioning system) and at the beam geometry level (e.g. spot size, shape and positional accuracy as a function of gantry angle and energy). A beam model is then generated in the treatment planning systems (TPS), and an extensive validation is needed, from simple geometries to heterogenous phantoms mimicking a patient. Last but not least, planning techniques ensuring plan robustness with respect to setup error and range uncertainties should be implemented in order to minimize the difference between planned and delivered dose distribution.

Impact of dose engine algorithm in pencil beam scanning proton therapy for breast cancer

PURPOSE Proton therapy for the treatment of breast cancer is acquiring increasing interest, due to the potential reduction of radiation-induced side effects such as cardiac and pulmonary toxicity. While several in silico studies demonstrated the gain in plan quality offered by pencil beam scanning (PBS) compared to passive scattering techniques, the related dosimetric uncertainties have been poorly investigated so far. METHODS Five breast cancer patients were planned with Raystation 6 analytical pencil beam (APB) and Monte Carlo (MC) dose calculation algorithms. Plans were optimized with APB and then MC was used to recalculate dose distribution. Movable snout and beam splitting techniques (i.e. using two sub-fields for the same beam entrance, one with and the other without the use of a range shifter) were considered. PTV dose statistics were recorded. The same planning configurations were adopted for the experimental benchmark. Dose distributions were measured with a 2D array of ionization chambers and compared to APB and MC calculated ones by means of a γ analysis (agreement criteria 3%, 3 mm). RESULTS Our results indicate that, when using proton PBS for breast cancer treatment, the Raystation 6 APB algorithm does not allow obtaining sufficient accuracy, especially with large air gaps. On the contrary, the MC algorithm resulted into much higher accuracy in all beam configurations tested and has to be recommended. CONCLUSIONS Centers where a MC algorithm is not yet available should consider a careful use of APB, possibly combined with a movable snout system or in any case with strategies aimed at minimizing air gaps.

Role of new radiation techniques in the treatment of pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm arising from the surface serosal cells of the pleural cavity. Surgery remains the main therapeutic standard in the treatment of MPM with the goal of complete gross cytoreduction of the tumor. Because MPM is a diffuse disease affecting the entire mesothelial lining of the hemithorax, surgery alone can rarely achieve adequate tumor‐free resection margins. The surgical choices are pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP). Radiotherapy (RT) is usually applied postoperatively with the aim to improve local control. However, the efficacy of RT is limited by the large volume of the target to be irradiated (tumor and pleural cavity) and the radiosensitivity of the nearby organs (heart, liver, lung, spinal cord, and esophagus). These factors have historically limited the effective radiation doses that can be given to the patient. There is no role for radical RT alone, but the role of RT as part of multimodality therapy is discussed. After EPP adjuvant RT to the entire hemithorax can reduce the recurrence rate and is well tolerated if strict limits to the dose to contralateral lung are applied: the V20 and V5 (the percent volume of the lung receiving more than 20Gy and 5Gy of radiation) correlate with increased lung toxicity. The use of modern sophisticated techniques allows good target coverage, more conformal high dose delivery, and clinically relevant normal tissue sparing.