| 71. |
- Olofsson, Jörgen, 1970-
(författare)
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Developing and evaluating dose calculation models for verification of advanced radiotherapy
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A prerequisite for modern radiotherapy is the ability to accurately determine the absorbed dose (D) that is given to the patient. The subject of this thesis has been to develop and evaluate efficient dose calculation models for high-energy photon beams delivered by linear accelerators. Even though the considered calculation models are general, the work has been focused on quality assurance (QA) tools used to independently verify the dose for individual treatment plans. The purpose of this verification is to guarantee patient safety and to improve the treatment outcome. Furthermore, a vital part of this work has been to explore the prospect of estimating the dose calculation uncertainties associated with individual treatment setups. A discussion on how such uncertainty estimations can facilitate improved clinical QA procedures by providing appropriate action levels has also been included within the scope of this thesis. In order to enable efficient modelling of the physical phenomena that are involved in dose output calculations it is convenient to divide them into two main categories; the first one dealing with the radiation exiting the accelerator’s treatment head and a second one associated with the subsequent energy deposition processes. A multi-source model describing the distribution of energy fluence emitted from the treatment head per delivered monitor unit (MU) is presented and evaluated through comparisons with measurements in multiple photon beams and collimator settings. The calculations show close agreement with the extensive set of experimental data, generally within +/-1% of corresponding measurements. The energy (dose) deposition in the irradiated object has been modelled through a photon pencil kernel solely based on a beam quality index (TPR20,10). This model was evaluated in a similar manner as the multi-source model at three different treatment depths. A separate study was focused on the specific difficulties associated with dose calculations in points located at a distance from the central beam axis. Despite the minimal input data required to characterize individual photon beams, the accuracy proved to be very good when comparing the calculated results with experimental data. The evaluated calculation models were finally used to analyse how well the lateral dose distributions from typical megavoltage photon beams are optimized with respect to the resulting beam flatness characteristics. The results did not reveal any obvious reasons why different manufacturers should provide different lateral dose distributions. Furthermore, the performed lateral optimizations indicate that there is room for improved flatness performance for the investigated linear accelerators.
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| 72. |
- Ottosson, Rickard, et al.
(författare)
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The feasibility of using Pareto fronts for comparison of treatment planning systems and delivery techniques
- 2009
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:2, s. 233-237
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Tidskriftsartikel (refereegranskat)abstract
- Pareto optimality is a concept that formalises the trade-off between a given set of mutually contradicting objectives. A solution is said to be Pareto optimal when it is not possible to improve one objective without deteriorating at least one of the other. A set of Pareto optimal solutions constitute the Pareto front. The Pareto concept applies well to the inverse planning process, which involves inherently contradictory objectives, high and uniform target dose on one hand, and sparing of surrounding tissue and nearby organs at risk (OAR) on the other. Due to the specific characteristics of a treatment planning system (TPS), treatment strategy or delivery technique, Pareto fronts for a given case are likely to differ. The aim of this study was to investigate the feasibility of using Pareto fronts as a comparative tool for TPSs, treatment strategies and delivery techniques. In order to sample Pareto fronts, multiple treatment plans with varying target conformity and dose sparing of OAR were created for a number of prostate and head neck IMRT cases. The DVHs of each plan were evaluated with respect to target coverage and dose to relevant OAR. Pareto fronts were successfully created for all studied cases. The results did indeed follow the definition of the Pareto concept, i.e. dose sparing of the OAR could not be improved without target coverage being impaired or vice versa. Furthermore, various treatment techniques resulted in distinguished and well separated Pareto fronts. Pareto fronts may be used to evaluate a number of parameters within radiotherapy. Examples are TPS optimization algorithms, the variation between accelerators or delivery techniques and the degradation of a plan during the treatment planning process. The issue of designing a model for unbiased comparison of parameters with such large inherent discrepancies, e.g. different TPSs, is problematic and should be carefully considered. fc.
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| 73. |
- Persson, Bertil R, et al.
(författare)
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“Abscopal” Effect of Radiation Therapy Combined with Immune-Therapy Using IFN-γ Gene Transfected Syngeneic Tumor Cells, in Rats with Bilateral Implanted N29 Tumors
- 2011
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Ingår i: ISRN Immunology. - : Hindawi Limited. - 2090-5645 .- 2090-5653. ; 2011
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Tidskriftsartikel (refereegranskat)abstract
- The tumor growth rate response was studied on N29 rat glioma tumor cells subcutaneously implanted on both hind legs of Fischer-344 rats. At around 30 days after inoculation, RT was given with 60Co gamma radiation with 4 daily fractions of 5 Gy only to the right-lateral tumors. At days 26, 42, and 54 after inoculation, immunization was performed with irradiated syngeneic IFNγ-gene transfected cells. Tumor growth rate (TGR % per day) of the right-lateral irradiated tumor was significantly decreased (P<0.01) after RT alone and with the combination of RT and immunization. But immunization alone gave no significant decrease of the TGR but significantly increased time of survival. The TGR of the unirradiated left-lateral tumors was significantly decreased (P<0.02) only in the group of rats treated with RT alone. It is apparent that tumor cells killed by the radiation mediate suppression of tumor cells outside the target area. This effect is called the abscopal effect.
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| 74. |
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| 75. |
- Persson, Bertil R, et al.
(författare)
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Immunization with syngeneic interferon-gamma (IFN-g) secreting tumour cells enhance the Therapeutic effect and Abscopal effect from combined treatment of subcutaneously implanted contra-lateral N29 tumours on Fischer rats with Pulsed electric fields (PEF) and 60Co-gamma radiation.
- 2014
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Ingår i: Acta Scientiarum Lundensia. - 1651-5013. ; 2014:002, s. 1-30
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study is to study the Abscopal regression of subcutaneously implanted N29 rat glioma after immunization with syngeneic IFNg secreting cells and treatment of contra-lateral tumours with pulsed electric fields (PEF) and/or radiation therapy (RT). The study was performed on rats of the Fischer-344 strain with rat glioma N29 tumours implanted subcutaneously on the flank or on both the right treated hind leg and the left untreated hind leg. Once weekly for three weeks, the animals were given intra-peritoneal injections of irradiated, modified N29 tumour cells, secreting interferon-gamma (IFN-g). PEF was given with 16 exponentially decaying pulses at a maximum electric fields strength of 1400 V/cm and t1/e= 1 ms. RT was given with 60Co gamma radiation at daily fractions of 5 Gy, to a total absorbed dose of 20 Gy. The animals were arranged into controls and groups of various treatments: PEF, RT, PEF+RT and immunization (IFNg). Fitting the data obtained from consecutive measurements of tumour volume (TV) of each individual tumour to an exponential model TV = TV0*exp[TGR*t] estimated the tumours growth rate (TGR %per day) after the day of treatment (t = 0). TGR of the right-lateral treated tumour was significantly decreased for independent treatments with PEF and RT and with the combined treatment PEF+RT. With immunization (IFNg) alone and in combination with PEF there was, however, no significant decrease of the TGR of the right-lateral tumours. But in the combination of immunization with RT or PEF+RT there was a highly significant decrease of the TGR values. The Abscopal effect was evaluated by comparing the growth rate of the untreated contra lateral tumours with the treated tumours. TGR of the left-lateral untreated tumour in the groups with independent treatment of right-lateral tumours with PEF, was not significantly reduced. But the TGR values are significantly reduced in the group of rats treated with RT and the combination PEF + RT. With IFNg alone and in combinations with PEF or RT there was no significant decrease of the TGR in the left lateral tumours. But in the combination of IFNg with PEF+RT there was a highly significant decrease of the TGR values in the left lateral tumours. The specific therapeutic effect (STE = 1 - TGRExposed/ TGRCtrl ) after treatments with PEF was 0.30±0.01 and after RT 0.46±0.04 and after the combination PEF+RT 0.36+/- 0.08. After immunization with IFNg secreting tumour cells the STE 0.09+/- 0.07 is not significantly different from zero. Also for the combination of immunization and PEF the STE value of 0.07+/- 0.07 is not significantly different from zero. In the combination of immunization with RT the STE value was 0.32+/- 0.01 that is significantly different from zero and only slightly lower than for RT alone. The STE of the combination of immunization with (PEF+RT) resulted in an unexpectedly high STE value of 0.70+/- 0.08 that is highly significantly different from zero (p < 0.0001). The specific Abscopal effect (SAE = 1 - TGRUn-Exposed/ TGRCtrl ) of the contra lateral unexposed tumours in rats treated with PEF or RT are both significantly different from zero. For RT the average SAE value is 0.33+/- 0.04 and for PEF it is 0.11+/- 0.05. The SAE value for the combined treatment with PEF + RT is 0.26+/- 0.02 that is about the same as for RT alone. For immunization with IFNg secreting tumour cells only and IFNg +PEF the SAE values were not significantly different from zero. But IFNg combined with RT result in a SAE value of 0.18±0.12 and the combination of IFNg with PEF+RT results in an improved abscopal effect with the SAE value of 0.33+/- 0.06. After combined treatment with PEF + RT the average of the therapeutic enhancement ratio (TER = STEExperimental / STEIndependent) is 0.47 +/- 0.12 and the abscopal enhancement ratio (AER = SAEExperimental / SAEIndependent) is 0.61 +/- 0.1 respectively. With all three treatment modalities combined IFNg + PEF + RT and all combinations of independent treatments with PEF, RT or IFNg are considered, the average of the TER is 1.20+/- 0.15 and AER is 1.22+/- 0.20. This might indicate that there is a synergism on the tumours on both sides by combining PEF, RT and immunization with IFNg secreting cells. These results were first presented Nov 21-24, 2002, as Poster at Society of Neuro-Oncology (SNO) Annual Meeting, San Diego, USA (Persson et al 2002).
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| 76. |
- Persson, Bertil R, et al.
(författare)
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Radiation immunomodulatory gene tumor therapy of rats with intracerebral glioma tumors.
- 2010
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Ingår i: Radiation Research. - 0033-7587. ; 173:4, s. 433-440
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Tidskriftsartikel (refereegranskat)abstract
- Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumors, single-fraction radiation therapy with 5 or 15 Gy had no significant effect on the survival time. Immunization with IFN-gamma-transfected N29 cells significantly increased the survival time by 61%. Single-fraction radiation therapy with 5 Gy combined with immunization increased the survival time significantly by 87% and complete remissions by 75% while with 15 Gy the survival time increased 45% with 38% complete remissions. For intracerebral N32 tumors, single-fraction radiation therapy with 15 Gy increased the survival time significantly by 20%. Immunization by itself had no significant effect with IFN-gamma-transfected N32 cells, but combined with 15 Gy single-fraction radiation therapy it increased survival time significantly by 40%, although there were no complete remissions. Based on these findings, we suggest a new therapeutic regimen for malignant glioma using single-fraction radiation therapy with a target absorbed dose of the order of 5-10 Gy combined with clinically verified immunotherapy.
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| 77. |
- Persson, Bertil R, et al.
(författare)
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Survival of rats with N29 brain tumours after irradiation with 5 or 15 Gy and immunization with IFN-gamma secreting tumour cells
- 2008
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Ingår i: BioMedical Engineering and Informatics : New Development and the Future - Proceedings of the 1st International Conference on BioMedical Engineering and Informatics, BMEI 2008 - New Development and the Future - Proceedings of the 1st International Conference on BioMedical Engineering and Informatics, BMEI 2008. - 9780769531182 ; 2, s. 243-247
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Konferensbidrag (refereegranskat)abstract
- Intra cerebral tumours were inoculated into the brain of Fischer-344 syngeneic rats. After one week they were treated with either 5 or 15 Gy of Co-60-gamma radiation. The first immunization was given 1 hour before the radiation treatment and then two more times with 14-day intervals. Immunization was performed with 3 x 10(6) radiation sterilized IFN-gamma secreting tumour cells (N29) injected intraperitoneally. Neither radiation therapy with 5 or 15 Gy nor immunization with N29 cells alone had any significant effect on the length of survival of N29 tumour bearing rats. But radiation therapy with 5 Gy combined with immunization with IFN-gamma secreting syngeneic N29 cells resulted in 63 % complete remissions and significantly (p < 0.05) increased survival for the tumour bearing rats. Corresponding combination with 15 Gy RT resulted in 50% complete remissions. There is a possibility of a synergistic effect by optimal combination of radiation therapy and immunization.
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| 78. |
- Petersson, Kristoffer, et al.
(författare)
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A clinical distance measure for evaluating treatment plan quality difference with Pareto fronts in radiotherapy
- 2017
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 3, s. 53-56
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Tidskriftsartikel (refereegranskat)abstract
- We present a clinical distance measure for Pareto front evaluation studies in radiotherapy, which we show strongly correlates (r = 0.74 and 0.90) with clinical plan quality evaluation. For five prostate cases, sub-optimal treatment plans located at a clinical distance value of >0.32 (0.28–0.35) from fronts of Pareto optimal plans, were assessed to be of lower plan quality by our (12) observers (p < .05). In conclusion, the clinical distance measure can be used to determine if the difference between a front and a given plan (or between different fronts) corresponds to a clinically significant plan quality difference.
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| 79. |
- Petersson, Kristoffer, et al.
(författare)
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Beam commissioning and measurements validating the beam model in a new TPS that converts helical tomotherapy plans to step-and-shoot IMRT plans.
- 2011
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Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 38:1, s. 40-46
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Tidskriftsartikel (refereegranskat)abstract
- A new type of treatment planning system called SHAREPLAN has been studied, which enables the transfer of treatment plans generated for helical tomotherapy delivery to plans that can be delivered on C-arm linacs. The purpose is to ensure continuous patient treatment during periods of unscheduled downtime for the TomoTherapy unit, particularly in clinics without a backup unit. The purpose of this work was to verify that the plans generated in this novel planning system are deliverable and accurate. The work consists primarily of beam commissioning, verification of the beam model, and measurements verifying that generated plans are deliverable with sufficient accuracy.
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| 80. |
- Petersson, Kristoffer, et al.
(författare)
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Conversion of helical tomotherapy plans to step-and-shoot IMRT plans-Pareto front evaluation of plans from a new treatment planning system
- 2011
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Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 38:6, s. 3130-3138
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The resulting plans from a new type of treatment planning system called SharePlan (TM) 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 SharePlan 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. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3592934]
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