Armin Lühr

Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

PURPOSE The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. METHODS AND MATERIALS For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. RESULTS Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. CONCLUSIONS Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

LET-painting increases tumour control probability in hypoxic tumours

Abstract LET-painting was suggested as a method to overcome tumour hypoxia. In vitro experiments have demonstrated a well-established relationship between the oxygen enhancement ratio (OER) and linear energy transfer (LET), where OER approaches unity for high-LET values. However, high-LET radiation also increases the risk for side effects in normal tissue. LET-painting attempts to restrict high-LET radiation to compartments that are found to be hypoxic, while applying lower LET radiation to normoxic tissues. Methods. Carbon-12 and oxygen-16 ion treatment plans with four fields and with homogeneous dose in the target volume, are applied on an oropharyngeal cancer case with an identified hypoxic entity within the tumour. The target dose is optimised to achieve a tumour control probability (TCP) of 95% when assuming a fully normoxic tissue. Using the same primary particle energy fluence needed for this plan, TCP is recalculated for three cases assuming hypoxia: first, redistributing LET to match the hypoxic structure (LET-painting). Second, plans are recalculated for varying hypoxic tumour volume in order to investigate the threshold volume where TCP can be established. Finally, a slight dose boost (5–20%) is additionally allowed in the hypoxic subvolume to assess its impact on TCP. Results. LET-painting with carbon-12 ions can only achieve tumour control for hypoxic subvolumes smaller than 0.5 cm3. Using oxygen-16 ions, tumour control can be achieved for tumours with hypoxic subvolumes of up to 1 or 2 cm3. Tumour control can be achieved for tumours with even larger hypoxic subvolumes, if a slight dose boost is allowed in combination with LET-painting. Conclusion. Our findings clearly indicate that a substantial increase in tumour control can be achieved when applying the LET-painting concept using oxygen-16 ions on hypoxic tumours, ideally with a slight dose boost.

Optimizing SHIELD-HIT for carbon ion treatment

The SHIELD-HIT Monte Carlo transport code has been widely used in particle therapy, but has previously shown some discrepancies, when compared with experimental data. In this work, the inelastic nuclear cross sections of SHIELD-HIT are calibrated to experimental data for carbon ions. In addition, the models for nuclear fragmentation were adjusted to experiments, for the partial charge-changing cross section of carbon ions in water. Comparison with fragmentation yield experiments for carbon and neon primaries were made for validation. For carbon primaries, excellent agreement between simulation and experiment was observed, with only minor discrepancies. For neon primaries, the agreement was also good, but larger discrepancies were observed, which require further investigation. In conclusion, the current version SHIELD-HIT10A is well suited for simulating problems arising in particle therapy for clinical ion beams.

Stopping power for particle therapy: the generic library libdEdx and clinically relevant stopping-power ratios for light ions.

Abstract Purpose: Stopping-power data enter at a number of different places in particle therapy and their uncertainties have a direct impact on the accuracy of the therapy, e.g., in treatment planning. Furthermore, for clinical quality assurance, the particle beam stopping-power ratios (STPR) have to be known accurately for dosimetry. Methods: An open-source computer library called libdEdx (library for energy loss per unit path length, dE/dx, calculations) is developed, providing stopping-power data from data tables and computer programs as well as a stopping-power formula comprising a large list of target materials. Calculations of STPR in the case of spread-out Bragg-peaks (SOBP) are performed with the Monte Carlo transportation code SHIELD-HIT (SHIELD-Heavy Ion Transport) using different ions relevant for particle therapy. Results: For SOBP the water-to-air STPR depends on the residual range and is qualitatively very similar for different ions; however, small quantitative differences exist between the considered ion species. Conclusions: libdEdx allows for a convenient and efficient treatment of stopping powers in numerical applications. It can be applied to estimate the dependence on the accuracy of the stopping power and to provide data for an extended number of target materials. The STPR for SOBP for different ions are found to be qualitatively the same which may allow for an analytical description valid for all ions.

Fluence correction factors and stopping power ratios for clinical ion beams

Abstract Background. In radiation therapy, the principal dosimetric quantity of interest is the absorbed dose to water. Therefore, a dose conversion to dose to water is required for dose deposited by ion beams in other media. This is in particular necessary for dose measurements in plastic phantoms for increased positioning accuracy, graphite calorimetry being developed as a primary standard for dose to water dosimetry, but also for the comparison of dose distributions from Monte Carlo simulations with those of pencil beam algorithms. Material and methods. In the conversion of absorbed dose to phantom material to absorbed dose to water the water-to-material stopping power ratios (STPR) and the fluence correction factors (FCF) for the full charged particle spectra are needed. We determined STPR as well as FCF for water to graphite, bone (compact), and PMMA as a function of water equivalent depth, zw, with the Monte Carlo code SHIELD-HIT10A. Simulations considering all secondary ions were performed for primary protons as well as carbon, nitrogen and oxygen ions with a total range of 3 cm, 14.5 cm and 27 cm as well as for two spread-out Bragg-peaks (SOBP). STPR as a function of depth are also compared to a recently proposed analytical formula. Results. The STPR are of the order of 1.022, 1.070, and 1.112 for PMMA, bone, and graphite, respectively. STPR vary only little with depth except close to the total range of the ion and they can be accurately approximated with an analytical formula. The amplitude of the FCF depends on the non-elastic nuclear interactions and it is unity if these interactions are turned off in the simulation. Fluence corrections are of the order of a percent becoming more pronounced for larger depths resulting in dose difference of the order of 5% around 25 cm. The same order of magnitude is observed for SOBP. Conclusions. We conclude that for ions with small total range (zw-eq ≤3 cm) dosimetry without applying FCF could in principle be performed in phantoms of materials other than water without a significant loss of accuracy. However, in clinical high-energy ion beams with penetration depths zw-eq ≥3 cm, where accurate positioning in water is not an issue, absorbed dose measurements should be directly performed in water or accurate values of FCF need to be established.

NTCP reduction for advanced head and neck cancer patients using proton therapy for complete or sequential boost treatment versus photon therapy.

ABSTRACT Background. To determine by treatment plan comparison differences in toxicity risk reduction for patients with head and neck squamous cell carcinoma (HNSCC) from proton therapy either used for complete treatment or sequential boost treatment only. Materials and methods. For 45 HNSCC patients, intensity-modulated photon (IMXT) and proton (IMPT) treatment plans were created including a dose escalation via simultaneous integrated boost with a one-step adaptation strategy after 25 fractions for sequential boost treatment. Dose accumulation was performed for pure IMXT treatment, pure IMPT treatment and for a mixed modality treatment with IMXT for the elective target followed by a sequential boost with IMPT. Treatment plan evaluation was based on modern normal tissue complication probability (NTCP) models for mucositis, xerostomia, aspiration, dysphagia, larynx edema and trismus. Individual NTCP differences between IMXT and IMPT (∆NTCPIMXT-IMPT) as well as between IMXT and the mixed modality treatment (∆NTCPIMXT-Mix) were calculated. Results. Target coverage was similar in all three scenarios. NTCP values could be reduced in all patients using IMPT treatment. However, ∆NTCPIMXT-Mix values were a factor 2–10 smaller than ∆NTCPIMXT-IMPT. Assuming a threshold of ≥ 10% NTCP reduction in xerostomia or dysphagia risk as criterion for patient assignment to IMPT, less than 15% of the patients would be selected for a proton boost, while about 50% would be assigned to pure IMPT treatment. For mucositis and trismus, ∆NTCP ≥ 10% occurred in six and four patients, respectively, with pure IMPT treatment, while no such difference was identified with the proton boost. Conclusions. The use of IMPT generally reduces the expected toxicity risk while maintaining good tumor coverage in the examined HNSCC patients. A mixed modality treatment using IMPT solely for a sequential boost reduces the risk by 10% only in rare cases. In contrast, pure IMPT treatment may be reasonable for about half of the examined patient cohort considering the toxicities xerostomia and dysphagia, if a feasible strategy for patient anatomy changes is implemented.

Analytical expressions for water-to-air stopping-power ratios relevant for accurate dosimetry in particle therapy

In particle therapy, knowledge of the stopping-power ratio (STPR) of the ion beam for water and air is necessary for accurate ionization chamber dosimetry. Earlier work has investigated the STPR for pristine carbon ion beams, but here we expand the calculations to a range of ions (1 ≤ z ≤ 18) as well as spread-out Bragg peaks (SOBPs) and provide a theoretical in-depth study with a special focus on the parameter regime relevant for particle therapy. The Monte Carlo transport code SHIELD-HIT is used to calculate complete particle-fluence spectra which are required for determining the STPR according to the recommendations of the International Atomic Energy Agency. The STPR at a depth d depends primarily on the average energy of the primary ions at d rather than on their charge z or absolute position in the medium. However, STPRs for different sets of stopping-power data for water and air recommended by the International Commission on Radiation Units and Measurements are compared, including also the recently revised data for water, yielding deviations up to 2% in the plateau region. In comparison, the influence of the secondary particle spectra on the STPR is about two orders of magnitude smaller in the whole region up till the practical range. The gained insights enable us to propose simple analytical expressions for the STPR for both pristine and SOBPs as a function of penetration depth depending parametrically on the practical range.

Recent improvements in the SHIELD-HIT code.

Abstract Purpose: The SHIELD-HIT Monte Carlo particle transport code has previously been used to study a wide range of problems for heavy-ion treatment and has been benchmarked extensively against other Monte Carlo codes and experimental data. Here, an improved version of SHIELD-HIT is developed concentrating on three objectives, namely: Enhanced functionality, improved efficiency, and a modification of employed physical models. Methodological developments: SHIELD-HIT (currently at version ‘10A’) is now equipped with an independent detector geometry, ripple filter implementations, and it is capable of using accelerator control files as a basis for the primaries. Furthermore, the code has been parallelized and efficiency is improved. The physical description of inelastic ion collisions has been modified. Results: The simulation of an experimental depth-dose distribution including a ripple filter reproduces experimental measurements with high accuracy. Conclusions: SHIELD-HIT is now faster, more user-friendly and accurate, and has an enhanced functionality with some features being currently unique to SHIELD-HIT. The possibility of data file exchange with existing treatment planning software for heavy-ion therapy allows for benchmarking under treatment conditions as well as extending the capabilities of treatment planning software.

Concept for individualized patient allocation: ReCompare--remote comparison of particle and photon treatment plans.

BackgroundIdentifying those patients who have a higher chance to be cured with fewer side effects by particle beam therapy than by state-of-the-art photon therapy is essential to guarantee a fair and sufficient access to specialized radiotherapy. The individualized identification requires initiatives by particle as well as non-particle radiotherapy centers to form networks, to establish procedures for the decision process, and to implement means for the remote exchange of relevant patient information. In this work, we want to contribute a practical concept that addresses these requirements.MethodsWe proposed a concept for individualized patient allocation to photon or particle beam therapy at a non-particle radiotherapy institution that bases on remote treatment plan comparison. We translated this concept into the web-based software tool ReCompare (REmote COMparison of PARticlE and photon treatment plans).ResultsWe substantiated the feasibility of the proposed concept by demonstrating remote exchange of treatment plans between radiotherapy institutions and the direct comparison of photon and particle treatment plans in photon treatment planning systems. ReCompare worked with several tested standard treatment planning systems, ensured patient data protection, and integrated in the clinical workflow.ConclusionsOur concept supports non-particle radiotherapy institutions with the patient-specific treatment decision on the optimal irradiation modality by providing expertise from a particle therapy center. The software tool ReCompare may help to improve and standardize this personalized treatment decision. It will be available from our website when proton therapy is operational at our facility.

SHIELD-HIT12A - a Monte Carlo particle transport program for ion therapy research

Purpose: The Monte Carlo (MC) code SHIELD-HIT simulates the transport of ions through matter. Since SHIELD-HIT08 we added numerous features that improves speed, usability and underlying physics and thereby the user experience. The -A fork of SHIELD-HIT also aims to attach SHIELD-HIT to a heavy ion dose optimization algorithm to provide MC-optimized treatment plans that include radiobiology. Methods: SHIELD-HIT12A is written in FORTRAN and carefully retains platform independence. A powerful scoring engine is implemented scoring relevant quantities such as dose and track-average LET. It supports native formats compatible with the heavy ion treatment planning system TRiP. Stopping power files follow ICRU standard and are generated using the libdEdx library, which allows the user to choose from a multitude of stopping power tables. Results: SHIELD-HIT12A runs on Linux and Windows platforms. We experienced that new users quickly learn to use SHIELD-HIT12A and setup new geometries. Contrary to previous versions of SHIELD-HIT, the 12A distribution comes along with easy-to-use example files and an English manual. A new implementation of Vavilov straggling resulted in a massive reduction of computation time. Scheduled for later release are CT import and photon-electron transport. Conclusions: SHIELD-HIT12A is an interesting alternative ion transport engine. Apart from being a flexible particle therapy research tool, it can also serve as a back end for a MC ion treatment planning system. More information about SHIELD-HIT12A and a demo version can be found on http://www.shieldhit.org.