Marco Schwarz

RADIATION DOSE-VOLUME EFFECTS IN THE LARYNX AND PHARYNX

The dose-volume outcome data for RT-associated laryngeal edema, laryngeal dysfunction, and dysphagia, have only recently been addressed, and are summarized. For late dysphagia, a major issue is accurate definition and uncertainty of the relevant anatomical structures. These and other issues are discussed.

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.

Proton therapy in lung cancer: Clinical outcomes and technical issues. A systematic review

BACKGROUND AND PURPOSE To determine whether, according to the currently available literature, proton therapy (PT) has a role in the treatment of non-small-cell lung cancer (NSCLC), to assess its safety and efficacy and to evaluate the main technical issues specifically related to this treatment technique. MATERIALS AND METHODS During March 2007, two independent researchers conducted a systematic review of the current data on the treatment of NSCLC with PT. RESULTS In total, 113 reports were retrieved, 17 of which were included in the analysis. There were no prospective trials (randomized or non-randomized). Nine uncontrolled single-arm studies were available from three PT centers, providing clinical outcomes for 214 patients in total. These reports were mainly related to stage I-II tumors, with results comparable to those obtained with surgery, without significant toxicity. In addition, two papers were found that compared photon and proton dose distributions, which showed a potential for dose escalation and/or a sparing of the organ at risk with PT. Finally, six studies analyzed dosimetric and technical issues related with PT, mainly underlining the difficulties in designing dose distributions that are representative of the dose actually delivered during treatment. CONCLUSIONS Although from a physical point of view PT is a good option for the treatment of NSCLC, limited data are available on its application in the clinical practice. Furthermore, the application of PT to lung cancer does present technical challenges. Because of the small number of institutions involved in the treatment of this disease, number of patients, and methodological weaknesses of the trials it is therefore not possible to draw definitive conclusions about the superiority of PT with respect to the photon techniques currently available for the treatment of NSCLC.

Helical tomotherapy vs. intensity-modulated proton therapy for whole pelvis irradiation in high-risk prostate cancer patients: dosimetric, normal tissue complication probability, and generalized equivalent uniform dose analysis.

PURPOSE To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for high-risk prostate cancer (HRPCa) patients. METHODS AND MATERIALS The plans of 8 patients with HRPCa treated with HT were compared with IMPT plans with two quasilateral fields set up (-100°; 100°) and optimized with the Hyperion treatment planning system. Both techniques were optimized to simultaneously deliver 74.2 Gy/Gy relative biologic effectiveness (RBE) in 28 fractions on planning target volumes (PTVs)3-4 (P + proximal seminal vesicles), 65.5 Gy/Gy(RBE) on PTV2 (distal seminal vesicles and rectum/prostate overlapping), and 51.8 Gy/Gy(RBE) to PTV1 (pelvic lymph nodes). Normal tissue calculation probability (NTCP) calculations were performed for the rectum, and generalized equivalent uniform dose (gEUD) was estimated for the bowel cavity, penile bulb and bladder. RESULTS A slightly better PTV coverage and homogeneity of target dose distribution with IMPT was found: the percentage of PTV volume receiving ≥ 95% of the prescribed dose (V(95%)) was on average > 97% in HT and > 99% in IMPT. The conformity indexes were significantly lower for protons than for photons, and there was a statistically significant reduction of the IMPT dosimetric parameters, up to 50 Gy/Gy(RBE) for the rectum and bowel and 60 Gy/Gy(RBE) for the bladder. The NTCP values for the rectum were higher in HT for all the sets of parameters, but the gain was small and in only a few cases statistically significant. CONCLUSIONS Comparable PTV coverage was observed. Based on NTCP calculation, IMPT is expected to allow a small reduction in rectal toxicity, and a significant dosimetric gain with IMPT, both in medium-dose and in low-dose range in all OARs, was observed.

Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series

BACKGROUND AND PURPOSE To evaluate survival, locoregional control and toxicity in a series of 56 mesothelioma patients treated from May 2005 to May 2010 with post-operative radiotherapy after extrapleural pneumonectomy (EPP) in three Italian Institutions (Brescia, Florence, and Modena). MATERIAL AND METHODS Fifty-six patients treated with adjuvant radiotherapy (RT) after EPP were analyzed. Four patients were treated with 3DCRT, 50 with IMRT and two with helical tomotherapy. Forty-five to 50 Gy in 25 fractions were given to the affected hemithorax and to ipsilateral mediastinum, with a simultaneous integrated boost to the sites of microscopically involved margins up to 60 Gy in 20/56 cases. RESULTS Three year locoregional control (LRC), distant metastasis free (DMF), disease free (DF), disease specific (DSS) and overall survival (OS) rates are 90%, 66%, 57%, 62%, and 60%, respectively. CONCLUSION Postoperative RT with modern techniques is an effective method to obtain excellent local control and cure rates in mesothelioma patients submitted to EPP.

Helical tomotherapy and intensity modulated proton therapy in the treatment of early stage prostate cancer: A treatment planning comparison

PURPOSE To compare helical tomotherapy (HT) and intensity modulated proton therapy (IMPT) on early stage prostate cancer treatments delivered with simultaneous integrated boost (SIB) in moderate hypofractionation. MATERIAL/METHODS Eight patients treated with HT were replanned with two-field IMPT (2fIMPT) and five-field IMPT (5fIMPT), using a small pencil beam size (3 mm sigma). The prescribed dose was 74.3 Gy in 28 fractions on PTV1 (prostate) and PTV2 (proximal seminal vesicles), 65.5 Gy on PTV3 (distal seminal vesicles) and on the overlap between rectum and PTVs. RESULTS IMPT and HT achieved similar target coverage and dose homogeneity, with 5fIMPT providing the best results. The conformity indexes of IMPT were significantly lower for PTV1+2 and PTV3. Above 65 Gy, HT and IMPT were equivalent in the rectum, while IMPT spared the bladder and the penile bulb from 0 to 70 Gy. From 0 up to 60 Gy, IMPT dosimetric values were (much) lower for all OARs except the femur heads, where HT was better than 2fIMPT in the 25-35 Gy dose range. OARs mean doses were typically reduced by 30-50% by IMPT. NTCPs for the rectum were within 1% between the two techniques, except when the endpoint was stool frequency, where IMPT showed a small (though statistically significant) benefit. CONCLUSIONS HT and IMPT produce similar dose distributions in the target volume. The current knowledge on dose-effect relations does not allow to quantify the clinical impact of the large sparing of IMPT at medium-to-low doses.

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.

In-gantry or remote patient positioning? Monte Carlo simulations for proton therapy centers of different sizes

PURPOSE We estimated the potential advantage of remote positioning (RP) vs. in-room positioning (IP) for a proton therapy facility in terms of patient throughput. MATERIALS AND METHODS Monte Carlo simulations of facilities with one, two or three gantries were performed. A sensitivity analysis was applied by varying the imaging and setup correction system (ICS), the speed of transporters (for RP) and beam switching time. Possible advantages of using three couches (for RP) or of switching the beam between fields was also investigated. RESULTS For a single gantry facility, an average of 20% more patients could be treated using RP: ranging from +45%, if a fast transporter and slow ICS were simulated, to -14% if a slow transporter and fast ICS was simulated. For two gantries, about 10% more patients could be treated with RP, ranging from +32% (fast transporter, slow ICS) to -12% (slow transporter, fast ICS). The ability to switch beam between fields did not substantially influence the throughput. In addition, the use of three transporters showed increased delays and therefore a slight reduction of the fractions executables. For three gantries, RP and IP showed similar results. CONCLUSIONS The advantage of RP vs. IP strongly depends on ICS and the speed of the transporters. For RP to be advantageous, reduced transport times are required. The advantage of RP decreases with increasing number of gantries.

Comparison between manual and automatic segment generation in step-and-shoot IMRT of prostate cancer

PURPOSE To compare two methods to generate treatment plans for intensity-modulated radiotherapy (IMRT) of prostate cancer, delivered in a step-and-shoot mode. The first method uses fluence optimization (inverse planning) followed by conversion of the fluence weight map into a limited number of segments. In the second method, segments are manually assigned using a class solution (forward planning), followed by computer optimization of the segment weights. METHODS Treatment plans for IMRT, utilizing a simultaneous integrated boost, were created. Plans comprise a five-field technique to deliver 78 Gy to the prostate plus seminal vesicles. Five patients were evaluated. Optimization objectives of both planning approaches concerned dose coverage of the target volumes and the dose distribution in the rectal wall. The two methods were evaluated by comparing dose distributions, the complexity of the resulting plan and the time expenditure to generate and to deliver the plan. RESULTS For both planning approaches 99% of the target volumes received 95% of the prescribed dose, which complies with our planning objectives. Inverse planning resulted in more conformal dose distributions than forward planning (conformity index: 1.37 versus 1.51). Inverse planning reduced the dose to the rectal wall compared to a manually designed plan, albeit to a small extent. The theoretical probability of severe rectal proctitis and/or stenosis was reduced on average by 1.9% with inverse planning. Maximal sparing of the rectal wall was achieved with inverse planning for a patient whose target volume was partly wrapped around the rectum. The number of segments generated with inverse planning ranged between 33 and 52, and between 9 and 13 segments for manually created segments. CONCLUSION Dose coverage of the planning target volumes is adequate for both approaches of planning. Inverse planning results in slightly better dose distributions with respect to the rectal wall compared to manual planning, at the cost of an increase of the number of segments by a factor of 3.