Kristoffer Petersson

Conversion of helical tomotherapy plans to step-and-shoot IMRT plans--Pareto front evaluation of plans from a new treatment planning system.

PURPOSE The resulting plans from a new type of treatment planning system called SharePlan have been studied. This software allows for the conversion of treatment plans generated in a TomoTherapy system for helical delivery, into plans deliverable on C-arm linear accelerators (linacs), which is of particular interest for clinics with a single TomoTherapy unit. The purpose of this work was to evaluate and compare the plans generated in the SharePlan system with the original TomoTherapy plans and with plans produced in our clinical treatment planning system for intensity-modulated radiation therapy (IMRT) on C-arm linacs. In addition, we have analyzed how the agreement between SharePlan and TomoTherapy plans depends on the number of beams and the total number of segments used in the optimization. METHODS Optimized plans were generated for three prostate and three head-and-neck (H&N) cases in the TomoTherapy system, and in our clinical treatment planning systems (TPS) used for IMRT planning with step-and-shoot delivery. The TomoTherapy plans were converted into step-and-shoot IMRT plans in SharePlan. For each case, a large number of Pareto optimal plans were created to compare plans generated in SharePlan with plans generated in the Tomotherapy system and in the clinical TPS. In addition, plans were generated in SharePlan for the three head-and-neck cases to evaluate how the plan quality varied with the number of beams used. Plans were also generated with different number of beams and segments for other patient cases. This allowed for an evaluation of how to minimize the number of required segments in the converted IMRT plans without compromising the agreement between them and the original TomoTherapy plans. RESULTS The plans made in SharePlan were as good as or better than plans from our clinical system, but they were not as good as the original TomoTherapy plans. This was true for both the head-and-neck and the prostate cases, although the differences between the plans for the latter were small. The evaluation of the head-and-neck cases also showed that the plans generated in SharePlan were improved when more beams were used. The SharePlan Pareto front came close to the front for the TomoTherapy system when a sufficient number of beams were added. The results for plans generated with varied number of beams and segments demonstrated that the number of segments could be minimized with maintained agreement between SharePlan and TomoTherapy plans when 10-19 beams were used. CONCLUSIONS This study showed (using Pareto front evaluation) that the plans generated in Share-Plan are comparable to plans generated in other TPSs. The evaluation also showed that the plans generated in SharePlan could be improved with the use of more beams. To minimize the number of segments needed in a plan with maintained agreement between the converted IMRT plans and the original TomoTherapy plans, 10-19 beams should be used, depending on target complexity. SharePlan has proved to be useful and should thereby be a time-saving complement as a backup system for clinics with a single TomoTherapy system installed alongside conventional C-arm linacs.

Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s

This study shows for the first time that normal brain tissue toxicities after WBI can be reduced with increased dose rate. Spatial memory is preserved after WBI with mean dose rates above 100Gy/s, whereas 10Gy WBI at a conventional radiotherapy dose rate (0.1Gy/s) totally impairs spatial memory.

Haematological toxicity in adult patients receiving craniospinal irradiation – Indication of a dose-bath effect

BACKGROUND AND PURPOSE The purpose of this study was to investigate the correlation between the haematological toxicity observed in patients treated with craniospinal irradiation, and the dose distribution in normal tissue, specifically the occurrence of large volumes exposed to low dose. MATERIALS AND METHODS Twenty adult male patients were included in this study; eight treated with helical tomotherapy (HT), and twelve with three-dimensional conformal radiation therapy. The relative volume of red bone marrow and body that was exposed to low dose (i.e. the so-called dose bath) was evaluated and correlated with nadir blood values during treatment, i.e. the severity of anaemia, leukopaenia, and thrombocytopaenia. The correlation was tested for different dose levels representing the dose bath using the Pearson product-moment correlation method. RESULTS We found a significant correlation between the volume of red bone marrow exposed to low dose and the severity of thrombocytopaenia during treatment. Furthermore, for the HT patients, a significant correlation was found between the relative volume of the body exposed to low dose and the severity of anaemia and leukopenia. CONCLUSIONS The severity of haematological toxicity correlated with the fraction of red bone marrow or body that was exposed to low dose.

High dose‐per‐pulse electron beam dosimetry – A model to correct for the ion recombination in the Advanced Markus ionization chamber

Purpose: The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose‐per‐pulse electron beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two‐voltage‐analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen. Methods: Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source‐to‐surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose–response, in beams with varying dose rate/dose‐per‐pulse, with the chamber together with dose rate/dose‐per‐pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose‐per‐pulse (10−2 ≤ mean dose rate ≤ 103 Gy/s, 102 ≤ mean dose rate within pulse ≤ 107 Gy/s, 10−4 ≤ dose‐per‐pulse ≤ 101 Gy), which was achieved by independently varying the linac gun grid tension, and the SSD. Results: The results demonstrate how the ion collection efficiency of the chamber decreased as the dose‐per‐pulse increased, and that the ion recombination was dependent on the dose‐per‐pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose‐per‐pulse range, but only for a low polarizing chamber voltage (50 V). However, the two‐voltage‐analysis method and the Burns & McEwen equation only agreed with the data at low dose‐per‐pulse values (≤ 10−2 and ≤ 10−1 Gy, respectively). An empirical model of the ion recombination in the chamber was found by fitting a logistic function to the data. Conclusions: The ion collection efficiency of the Advanced Markus ionization chamber decreases for measurements in electron beams with increasingly higher dose‐per‐pulse. However, this chamber is still functional for dose measurements in beams with dose‐per‐pulse values up toward and above 10 Gy, if the ion recombination is taken into account. Our results show that existing models give a less‐than‐accurate description of the observed ion recombination. This motivates the use of the presented empirical model for measurements with the Advanced Markus chamber in high dose‐per‐pulse electron beams, as it enables accurate absorbed dose measurements (uncertainty estimation: 2.8–4.0%, k = 1). The model depends on the dose‐per‐pulse in the beam, and it is also influenced by the polarizing chamber voltage, with increasing ion recombination with a lowering of the voltage.

High dose‐per‐pulse electron beam dosimetry: Usability and dose‐rate independence of EBT3 Gafchromic films

Purpose: The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose‐per‐pulse linear accelerator (linac), capable of delivering electron beams with a mean dose‐rate (Dm) ranging from 0.07 to 3000 Gy/s and a dose‐rate in pulse (Dp) of up to 8 × 106 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose‐rate dependence of their response. Material and methods: Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Dm dependence was studied at the clinical linac by changing the pulse repetition frequency (f) of the beam in order to vary Dm between 0.55 and 4.40 Gy/min, while Dp dependence was probed at the prototype machine for Dp ranging from 7 × 103 to 8 × 106 Gy/s. Dp dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo‐luminescent dosimeters (TLD) that have been reported as being dose‐rate independent up to such high dose‐rates. Results: We report that uncertainty below 4% (k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Dm dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Dp range attainable at the prototype linac confirming the absence of any dose‐rate dependence within the investigated range (7 × 103 to 8 × 106 Gy/s). This aspect was further corroborated by the linear relationship between the dose‐per‐pulse (Dp) measured by films and the charge per pulse (Cp) measured at the prototype linac exit. Conclusion: Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% (k = 2) and are dose‐rate and energy independent.

Discrepancies between selected Pareto optimal plans and final deliverable plans in radiotherapy multi-criteria optimization

Multi-criteria optimization provides decision makers with a range of clinical choices through Pareto plans that can be explored during real time navigation and then converted into deliverable plans. Our study shows that dosimetric differences can arise between the two steps, which could compromise the clinical choices made during navigation.

Evaluation of dual-arc VMAT radiotherapy treatment plans automatically generated via dose mimicking.

Dose mimicking allows for the automatic creation and optimization of coplanar/non-coplanar three dimensional conformal radiation therapy (3DCRT), step-and-shoot intensitymodulated radiation therapy (IMRT), sliding window IMRT, and volumetric modulated arc therapy (VMAT) treatment plans that mimics a reference radiotherapy treatment plan of any modality. The algorithm is currently used in multi-criteria optimization (MCO) to go from a navigated fluence-based plan to a plan that is actually deliverable [1,2]. The algorithm is also used to create alternative treatment plans in various treatment planning systems (TPSs). Provided that the dose mimicking algorithm is capable of creating deliverable treatment plans of high plan quality, it would ensure a high level of flexibility in clinical practice. The dose mimicking algorithm would give clinics (with TPSs which have dose mimicking capabilities) the ability of automated multi-modality optimization, which could be used to verify that a patient is always treated with the optimal treatment technique [3]. It would also supply alternative treatment plans if a treatment technique/machine becomes unavailable, ensuring continuous patient treatment, which is of great importance for therapeutic outcome [4]. Hence, the purpose of this study was to investigate the plan quality achieved for dual-arc VMAT plans, optimized via dose mimicking. A second purpose was to verify that such plans can be accurately delivered at a clinically commissioned linear accelerator (linac).

Multi-modality optimisation in radiotherapy treatment planning using composite objective values

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Treatment plan comparison using grading analysis based on clinical judgment.

Abstract Purpose. In this work we explore a method named clinical grading analysis (CGA) which is based on clinical assessments performed by radiation oncologists (ROs). The purpose is to investigate how useful the method is for treatment plan comparisons, and how the CGA results correlate with dosimetric evaluation parameters, traditionally used for treatment plan comparisons. Material and methods. Helical tomotherapy (HTT) and seven-beam step-and-shoot intensity modulated radiation therapy (SS-IMRT) plans were compared and assessed by 10 experienced ROs for 23 patient cases. A CGA was performed where the plans were graded based on how the ROs thought they compared to each other. The resulting grades from the CGA were analyzed and compared to dose-volume statistics and equivalent uniform dose (EUD) data. Results. For eight of the 23 cases the CGA revealed a significant difference between the HTT and the SS-IMRT plans, five cases were in favor of HTT, and three in favor of SS-IMRT. Comparing the dose-volume statistics and EUD-data with the result from the CGA showed that CGA results correlated well with dose-volume statistics for cases regarding difference in target coverage or doses to organs at risk. The CGA results also correlated well with EUD-data for cases with difference in clinical target volume (CTV) coverage but the correlation for cases with difference in planning target volume (PTV) coverage was not as clear. Conclusions. This study presents CGA as a useful method of comparing radiotherapy treatment plans. The proposed method offers a formalized way of introducing and evaluating the implementation of new radiotherapy techniques in a clinical setting. The CGA identify patients that have a clinical benefit of one or the other of the advanced treatment techniques available to them, i.e. in this study HTT and SS-IMRT, which facilitates a more optimal use of a clinics’ advanced treatment resources.

The advantage of Flash radiotherapy confirmed in mini-pig and cat-cancer patients

Purpose: Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. Experimental Design: Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called “FLASH-RT” and irradiation delivered at a conventional dose rate called “Conv-RT.” A clinical, phase I, single-dose escalation trial (25–41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT. Results: Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%. Conclusions: Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients. See related commentary by Harrington, p. 3