Plan quality assessment in clinical practice: Results of the 2020 ESTRO survey on plan complexity and robustness.

PURPOSE: Plan complexity and robustness are two essential aspects of treatment plan quality but there is a great variability in their management in clinical practice. This study reports the results of the 2020 ESTRO survey on plan complexity and robustness to identify needs and guide future discussions and consensus. METHODS: A survey was distributed online to ESTRO members. Plan complexity was defined as the modulation of machine parameters and increased uncertainty in dose calculation and delivery. Robustness was defined as a dose distribution's sensitivity towards errors stemming from treatment uncertainties, patient setup, or anatomical changes. RESULTS: A total of 126 radiotherapy centres from 33 countries participated, 95 of them (75%) from Europe and Central Asia. The majority controlled and evaluated plan complexity using monitor units (56 centres) and aperture shapes (38 centres). To control robustness, 98 (97% of question responses) photon and 5 (50%) proton centres used PTV margins for plan optimization while 75 (94%) and 5 (50%), respectively, used margins for plan evaluation. Seventeen (21%) photon and 8 (80%) proton centres used robust optimisation, while 10 (13%) and 8 (80%), respectively, used robust evaluation. Primary uncertainties considered were patient setup (photons and protons) and range calculation uncertainties (protons). Participants expressed the need for improved commercial tools to control and evaluate plan complexity and robustness. CONCLUSION: Clinical implementation of methods to control and evaluate plan complexity and robustness is very heterogeneous. Better tools are needed to manage complexity and robustness in treatment planning systems. International guidelines may promote harmonization.

Technical challenges in the treatment of mediastinal lymphomas by proton pencil beam scanning and deep inspiration breath-hold.

PURPOSE: To comprehensively describe the treatment of mediastinal lymphoma by pencil beam scanning (PBS) proton therapy. METHODS: Fourteen patients underwent PBS proton treatment in a supine position in deep inspiration breath-hold (DIBH). Three DIBH computed tomography (CT) scans were acquired for each patient to delineate the Internal Target Volume (ITV). Intensity-modulated proton therapy (IMPT) was planned by min-max robust optimization on the ITV, with a 6 mm setup and 3.5% range uncertainties. Robustness analysis was performed and dose coverage was visually inspected on the corresponding voxel-wise minimum map. Layer repainting was set equal to 5 to compensate for cardiac motion. Intra-fraction reproducibility during treatment was assessed by repeated daily DIBH X-ray imaging. Finally, an additional CT was acquired at half treatment to estimate the impact of inter-fraction dosimetric reproducibility. RESULTS: IMPT guaranteed robust mediastinal target coverage and organs-at-risk sparing. However, visual voxel-wise robustness evaluation showed that in five patients a second optimization with focused objectives in the cost-function was necessary to achieve a robust coverage of the target regions at the interface between lungs and soft tissue. In six patients, repainting was not used due to excessive treatment time length and poor patient compliance. Intra-fraction average reproducibility was within 1 mm/1degree. On repeated CT scans, inter-fraction setup errors and/or anatomical changes showed minimal dosimetric differences in CTV coverage. CONCLUSION: IMPT in DIBH is effective and reproducible to treat mediastinal lymphomas. Caution is recommended to guarantee robust dose delivery to high-risk regions at the interface between lungs and soft tissue.

Methodologies to Increase the Level of Evidence of Real-life Proton Therapy in Head and Neck Tumors.

This review aims to present and assess available and new methodologies to increase the clinical evidence of proton therapy data for patients with head and neck cancer. Despite the increasing number of scientific reports showing the feasibility and effectiveness of proton therapy in head and neck cancer, clinical evidence on the potential benefits of its use remains low for several reasons. In this article, the pros and cons of consolidated and new methodologies in this setting such as randomized clinical trials, the model-based approach, and the use of prospective multicentric registries will be detailed.

Clinical implementation of pencil beam scanning proton therapy for liver cancer with forced deep expiration breath hold.

PURPOSE: To present our technique for liver cancer treatments with proton therapy in pencil beam scanning mode and to evaluate the impact of uncertainties on plan quality. MATERIALS AND METHODS: Seventeen patients affected by liver cancer were included in this study. Patients were imaged and treated in forced breath-hold using the Active Breathing Coordinator system and monitored with an optical tracking system. Three simulation CTs were acquired to estimate the anatomical variability between breath-holds and generate an internal target volume (ITV). The treatment plans were optimized with a Single Field Optimization technique aimed at minimizing the use of range shifter. Plan robustness was tested simulating systematic range and setup uncertainties, as well as the interplay effect between breath-holds. The appropriateness of margin was further verified based on the actual positioning data acquired during treatment. RESULTS: The dose distributions of the nominal plans achieved a satisfactory target coverage in 11 out of 17 patients, while in the remaining 6 D95 to the PTV was affected by the constraint on mean liver dose. The constraints for all other organs at risk were always within tolerances. The interplay effect had a limited impact on the dose distributions: the worst case scenario showed a D95 reduction in the ITV < 3.9 GyRBE and no OAR with D1 > 105% of the prescription dose. The robustness analysis showed that for 13 out of 17 patients the ITV coverage in terms of D95 was better than D95 of the PTV in the nominal plan. For the remaining 4 patients, the maximum difference between ITV D95 and PTV D95 was ≤0.7% even for the largest simulated setup error and it was deemed clinically acceptable. Hot spots in the OARs were always lower than 105% of the prescription dose. Positioning images confirmed that the breath hold technique and the PTV margin were adequate to compensate for inter- and intra-breath-hold variations in liver position. CONCLUSION: We designed and clinically applied a technique for the treatment of liver cancer with proton pencil beam scanning in forced deep expiration breath-hold. The initial data on plan robustness and patient positioning suggest that the choices in terms of planning technique and treatment margins are able to reach the desired balance between target coverage and organ at risk sparing.

Proton or photon radiosurgery for cardiac ablation of ventricular tachycardia? Breath and ECG gated robust optimization.

PURPOSE: Ventricular tachycardia (VT) is a life-threatening heart disorder. The aim of this preliminary study is to assess the feasibility of stereotactic body radiation therapy (SBRT) photon and proton therapy (PT) plans for the treatment of VT, adopting robust optimization technique for both irradiation techniques. METHODS: ECG gated CT images (in breath hold) were acquired for one patient. Conventional planning target volume (PTV) and robust optimized plans (25GyE in single fraction) were simulated for both photon (IMRT, 5 and 9 beams) and proton (SFO, 2 beams) plans. Robust optimized plans were obtained both for protons and photons considering in the optimization setup errors (5 mm in the three orthogonal directions), range (±3.5%) and the clinical target volume (CTV) motion due to heartbeat and breath-hold variability. RESULTS: The photon robust optimization method, compared to PTV-based plans, showed a reduction in the average dose to the heart by about 25%; robust optimization allowed also reducing the mean dose to the left lung from 3.4. to 2.8 Gy for 9-beams configuration and from 4.1 to 2.9 Gy for 5-beams configuration. Robust optimization with protons, allowed further reducing the OAR doses: average dose to the heart and to the left lung decreased from 7.3 Gy to 5.2 GyE and from 2.9 Gy to 2.2 GyE, respectively. CONCLUSIONS: Our study demonstrates the importance of the optimization technique adopted in the treatment planning system for VT treatment. It has been shown that robust optimization can significantly reduce the dose to healthy cardiac tissues and that PT further increases this gain.

What is plan quality in radiotherapy? The importance of evaluating dose metrics, complexity, and robustness of treatment plans.

Plan evaluation is a key step in the radiotherapy treatment workflow. Central to this step is the assessment of treatment plan quality. Hence, it is important to agree on what we mean by plan quality and to be fully aware of which parameters it depends on. We understand plan quality in radiotherapy as the clinical suitability of the delivered dose distribution that can be realistically expected from a treatment plan. Plan quality is commonly assessed by evaluating the dose distribution calculated by the treatment planning system (TPS). Evaluating the 3D dose distribution is not easy, however; it is hard to fully evaluate its spatial characteristics and we still lack the knowledge for personalising the prediction of the clinical outcome based on individual patient characteristics. This advocates for standardisation and systematic collection of clinical data and outcomes after radiotherapy. Additionally, the calculated dose distribution is not exactly the dose delivered to the patient due to uncertainties in the dose calculation and the treatment delivery, including variations in the patient set-up and anatomy. Consequently, plan quality also depends on the robustness and complexity of the treatment plan. We believe that future work and consensus on the best metrics for quality indices are required. Better tools are needed in TPSs for the evaluation of dose distributions, for the robust evaluation and optimisation of treatment plans, and for controlling and reporting plan complexity. Implementation of such tools and a better understanding of these concepts will facilitate the handling of these characteristics in clinical practice and be helpful to increase the overall quality of treatment plans in radiotherapy.

An avoidance method to minimize dose perturbation effects in proton pencil beam scanning treatment of patients with small high-Z implants.

To implement a multi-field-optimization (MFO) technique for treating patients with high-Z implants in pencil beam scanning proton-therapy and generate treatment plans that avoids small implants. Two main issues were addressed: (i) the assessment of the optimal CT acquisition and segmentation technique to define the dimension of the implant and (ii) the distance of pencil beams from the implant (avoidance margin) to assure that it does not affect dose distribution. Different CT reconstruction protocols (by O-MAR or standard reconstruction and by 12 bit or 16 bit dynamic range) followed by thresholding segmentation were tested on a phantom with lead spheres of different sizes. The proper avoidance margin was assessed on a dedicated phantoms of different materials (copper/tantalum and lead), shape (square slabs and spheres) and detectors (two-dimensional array chamber and radio-chromic films). The method was then demonstrated on a head-and-neck carcinoma patient, who underwent carotid artery embolization with a platinum coil close to the target. Regardless the application of O-MAR reconstruction, the CT protocol with a full 16 bit dynamic range allowed better estimation of the sphere volumes, with maximal error around -5% in the greater sphere only. Except the configuration with a shallow target (which required a pre-absorber), particularly with a retracted snout, an avoidance margin of around 0.9-1.3 cm allowed to keep the difference between planned and measured dose below 5-10%. The patient plan analysis showed adequate plan quality and confirmed effective implant avoidance. Potential target under-dosage can be produced by patient misalignment, which could be minimized by daily alignment on the implant, identifiable on orthogonal kilovolt images. By implant avoidance MFO it was possible to minimize potential dose perturbation effects produced by small high-Z implants. An advantage of such approach lies in its potential applicability for any type of implant, regardless the precise knowledge of its composition.

The Role of Plan Robustness Evaluation in Comparing Protons and Photons Plans - An Application on IMPT and IMRT Plans in Skull Base Chordomas.

PURPOSE: To analyze robustness of treatment plans optimized using different approaches in intensity modulated proton therapy (IMPT) and investigate the necessity of robust optimization and evaluation in intensity modulated radiotherapy (IMRT) plans for skull base chordomas. MATERIALS AND METHODS: Two photon plans, standard IMRT and robustly optimized IMRT (RB-IMRT), and two IMPT plans, robustly optimized multi field optimization (MFO) and hybrid-MFO (HB-MFO), were created in RayStation TPS for five patients previously treated using single field uniform optimization (SFO). Both set-up and range uncertainties were incorporated during robust optimization of IMPT plans whereas only set-up uncertainty was used in RB-IMRT. The dosimetric outcomes from the five planning techniques were compared for every patient using standard dose volume indices and integral dose (ID) estimated for target and organs at risk (OARs). Robustness of each treatment plan was assessed by introducing set-up uncertainties of ±3 mm along the three translational axes and, only in protons, an additional range uncertainty of ±3.5%. RESULTS: All the five nominal plans provided comparable and clinically acceptable target coverage. In comparison to nominal plans, worst case decrease in D95% of clinical target volume-high risk (CTV-HR) were 11.1%, 13.5%, and 13.6% for SFO, MFO, and HB-MFO plans respectively. The corresponding values were 13.7% for standard IMRT which improved to 11.5% for RB-IMRT. The worst case increased in high dose (D1%) to CTV-HR was highest in IMRT (2.1%) and lowest in SFO (0.7%) plans. Moreover, IMRT showed worst case increases in D1% for all neurological OARs and were lowest for SFO plans. The worst case D1% for brainstem, chiasm, spinal cord, optic nerves, and temporal lobes were increased by 29%, 41%, 30%, 41% and 14% for IMRT and 18%, 21%, 21%, 24%, and 7% for SFO plans, respectively. In comparison to IMRT, RB-IMRT improved D1% of all neurological OARs ranging from 5% to 14% in worst case scenarios. CONCLUSION: Based on the five cases presented in the current study, all proton planning techniques (SFO, MFO and HB-MFO) were robust both for target coverage and OARs sparing. Standard IMRT plans were less robust than proton plans in regards to high doses to neurological OARs. However, robust optimization applied to IMRT resulted in improved robustness in both target coverage and high doses to OARs. Robustness evaluation may be considered as a part of plan evaluation procedure even in IMRT.

Clinical implementation in proton therapy of multi-field optimization by a hybrid method combining conventional PTV with robust optimization.

To implement a robust multi-field optimization (MFO) technique compatible with the application of a Monte Carlo (MC) algorithm and to evaluate its robustness. Nine patients (three brain, five head-and-neck, one spine) underwent proton treatment generated by a novel robust MFO technique. A hybrid (hMFO) approach was implemented, planning dose coverage on isotropic PTV compensating for setup errors, whereas range calibration uncertainties are incorporated into PTV robust optimization process. hMFO was compared with single-field optimization (SFO) and full robust multi-field optimization (fMFO), both on the nominal plan and the worst-case scenarios assessed by robustness analysis. The SFO and the fMFO plans were normalized to hMFO on CTV to obtain iso-D95 coverage, and then the organs at risk (OARs) doses were compared. On the same OARs, in the normalized nominal plans the potential impact of variable relative biological effectiveness (RBE) was investigated. hMFO reduces the number of scenarios computed for robust optimization (from twenty-one in fMFO to three), making it practicable with the application of a MC algorithm. After normalizing on D95 CTV coverage, nominal hMFO plans were superior compared to SFO in terms of OARs sparing (p  < 0.01), without significant differences compared to fMFO. The improvement in OAR sparing with hMFO with respect to SFO was preserved in worst-case scenarios (p  < 0.01), confirming that hMFO is as robust as SFO to physical uncertainties, with no significant differences when compared to the worst case scenarios obtained by fMFO. The dose increase on OARs due to variable RBE was comparable to the increase due to physical uncertainties (i.e. 4-5 Gy(RBE)), but without significant differences between these techniques. hMFO allows improving plan quality with respect to SFO, with no significant differences with fMFO and without affecting robustness to setup, range and RBE uncertainties, making clinically feasible the application of MC-based robust optimization.

A pre-absorber optimization technique for pencil beam scanning proton therapy treatments.

PURPOSE: To implement a new proton therapy planning method for the treatment of shallow lesions with PBS and to compare it to the standard method. METHODS AND MATERIALS: In order to treat shallow lesions, a pre-absorber, usually called range-shifter (RS), is needed: it is used to degrade the beam energy and treat tumors shallower than the minimum range available. Its use is associated to dose calculation uncertainties and plan quality degradation which should be minimized. We studied five tumor localizations requiring RS and created three plans for each case: a) standard method with the RS close to the patient surface, b) with the RS used only for the shallow part of the tumor (when strictly needed) and completely retracted and c) as the b) approach but with the RS close to the patient. We called these two approaches 'Range Shifter Optimization' (RSO) techniques. We compared those plans in terms of dose distribution quality, delivery time and patient-specific-QA results. RESULTS: In most cases a good dose reduction to OARs with no significant loss in terms of target coverage was obtained when the RSO techniques were used. Patient-specific-QA gave very good results in terms of γ-Passing-Rate (PR) (3%, 3 mm) for both RSO techniques (mean 98.09%), while the standard had some very low PR (minimum 81.09%). The delivery time increased (5.0 min on average per treatment) but was still acceptable in terms of patient compliance. CONCLUSION: We developed a new planning technique for shallow lesions and we demonstrated its superiority in terms of both plan quality and patient-specific-QA results with respect to the standard method. This technique is routinely used to treat patients in our center.

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 lamb's 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 lamb's 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.

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.

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.

Systematic evaluation of three different commercial software solutions for automatic segmentation for adaptive therapy in head-and-neck, prostate and pleural cancer.

PURPOSE: To validate, in the context of adaptive radiotherapy, three commercial software solutions for atlas-based segmentation. METHODS AND MATERIALS: Fifteen patients, five for each group, with cancer of the Head&Neck, pleura, and prostate were enrolled in the study. In addition to the treatment planning CT (pCT) images, one replanning CT (rCT) image set was acquired for each patient during the RT course. Three experienced physicians outlined on the pCT and rCT all the volumes of interest (VOIs). We used three software solutions (VelocityAI 2.6.2 (V), MIM 5.1.1 (M) by MIMVista and ABAS 2.0 (A) by CMS-Elekta) to generate the automatic contouring on the repeated CT. All the VOIs obtained with automatic contouring (AC) were successively corrected manually. We recorded the time needed for: 1) ex novo ROIs definition on rCT; 2) generation of AC by the three software solutions; 3) manual correction of AC.To compare the quality of the volumes obtained automatically by the software and manually corrected with those drawn from scratch on rCT, we used the following indexes: overlap coefficient (DICE), sensitivity, inclusiveness index, difference in volume, and displacement differences on three axes (x, y, z) from the isocenter. RESULTS: The time saved by the three software solutions for all the sites, compared to the manual contouring from scratch, is statistically significant and similar for all the three software solutions. The time saved for each site are as follows: about an hour for Head&Neck, about 40 minutes for prostate, and about 20 minutes for mesothelioma. The best DICE similarity coefficient index was obtained with the manual correction for: A (contours for prostate), A and M (contours for H&N), and M (contours for mesothelioma). CONCLUSIONS: From a clinical point of view, the automated contouring workflow was shown to be significantly shorter than the manual contouring process, even though manual correction of the VOIs is always needed.

Is there a single spot size and grid for intensity modulated proton therapy? Simulation of head and neck, prostate and mesothelioma cases.

PURPOSE: To assess the quality of dose distributions in real clinical cases for different dimensions of scanned proton pencil beams. The distance between spots (i.e., the grid of delivery) is optimized for each dimension of the pencil beam. METHODS: The authors vary the σ of the initial Gaussian size of the spot, from σ(x) = σ(y) = 3 mm to σ(x) = σ(y) = 8 mm, to evaluate the impact of the proton beam size on the quality of intensity modulated proton therapy (IMPT) plans. The distance between spots, Δx and Δy, is optimized on the spot plane, ranging from 4 to 12 mm (i.e., each spot size is coupled with the best spot grid resolution). In our Hyperion treatment planning system (TPS), constrained optimization is applied with respect to the organs at risk (OARs), i.e., the optimization tries to satisfy the dose objectives in the planning target volume (PTV) as long as all planning objectives for the OARs are met. Three-field plans for a nasopharynx case, two-field plans for a prostate case, and two-field plans for a malignant pleural mesothelioma case are considered in our analysis. RESULTS: For the head and neck tumor, the best grids (i.e., distance between spots) are 5, 4, 6, 6, and 8 mm for σ = 3, 4, 5, 6, and 8 mm, respectively. σ ≤ 5 mm is required for tumor volumes with low dose and σ ≤ 4 mm for tumor volumes with high dose. For the prostate patient, the best grid is 4, 4, 5, 5, and 5 mm for σ = 3, 4, 5, 6, and 8 mm, respectively. Beams with σ > 3 mm did not satisfy our first clinical requirement that 95% of the prescribed dose is delivered to more than 95% of prostate and proximal seminal vesicles PTV. Our second clinical requirement, to cover the distal seminal vesicles PTV, is satisfied for beams as wide as σ = 6 mm. For the mesothelioma case, the low dose PTV prescription is well respected for all values of σ, while there is loss of high dose PTV coverage for σ > 5 mm. The best grids have a spacing of 6, 7, 8, 9, and 12 mm for σ = 3, 4, 5, 6, and 8 mm, respectively. CONCLUSIONS: The maximum acceptable proton pencil beam σ depends on the volume treated, the protocol of delivery, and optimization of the plan. For the clinical cases, protocol and optimization used in this analysis, acceptable σs are ≤ 4 mm for the head and neck tumor, ≤ 3 mm for the prostate tumor and ≤ 6 mm for the malignant pleural mesothelioma. One can apply the same procedure used in this analysis when given a "class" of patients, a σ and a clinical protocol to determine the optimal grid spacing.

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.

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.

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.

Intensity-modulated proton therapy versus helical tomotherapy in nasopharynx cancer: planning comparison and NTCP evaluation.

PURPOSE: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous integrated boost approach. METHODS AND MATERIALS: The data from 6 patients who had previously been treated with HT were used. A three-beam IMPT technique was optimized in the Hyperion treatment planning system, simulating a "beam scanning" technique. HT was planned using the tomotherapy treatment planning system. Both techniques were optimized to simultaneously deliver 66 Gy in 30 fractions to planning target volume (PTV1; GTV and enlarged nodes) and 54 Gy to PTV2 subclinical, electively treated nodes. Normal tissue complication probability calculation was performed for the parotids and larynx. RESULTS: Very similar PTVs coverage and homogeneity of the target dose distribution for IMPT and HT were found. The conformity index was significantly lower for protons than for photons (1.19 vs. 1.42, respectively). The mean dose to the ipsilateral and contralateral parotid glands decreased by 6.4 Gy and 5.6 Gy, respectively, with IMPT. The volume of mucosa and esophagus receiving > or =20 Gy and > or =30 Gy with IMPT was significantly lower than with HT. The average volume of larynx receiving > or =50 Gy was significantly lower with HT, while for thyroid, it was comparable. The volume receiving > or =30, > or =20, and > or =10 Gy in total body volume decreased with IMPT by 14.5%, 19.4%, and 23.1%, respectively. The normal tissue complication probability for the parotid glands was significantly lower with IMPT for all sets of parameters; however, we also estimated an almost full recovery of the contralateral parotid with HT. The normal tissue complication probability for the larynx was not significantly different between the two irradiation techniques. CONCLUSION: Excellent target coverage, homogeneity within the PTVs, and sparing of the organs at risk were reached with both modalities. IMPT allows for better sparing of most organs at risk at medium-to-low doses.

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.