Accuracy of absorbed dose in external photon beam radiotherapy : what level is sufficient and how to approach it?

Radiation therapy (RT) plays currently significant role in curative treatments of several cancers. External beam RT is carried out mostly by using megavoltage beams of linear accelerators. Tumor eradication and normal tissue complications correlate to dose absorbed in tissues. Normally this dependence is steep and it is crucial that actual dose within patient accurately correspond to the planned dose. All factors in a RT procedure contain uncertainties requiring strict quality assurance. From hospital physicist´s point of a view, technical quality control (QC), dose calculations and methods for verification of correct treatment location are the most important subjects. Most important factor in technical QC is the verification that radiation production of an accelerator, called output, is within narrow acceptable limits. The output measurements are carried out according to a locally chosen dosimetric QC program defining measurement time interval and action levels. Dose calculation algorithms need to be configured for the accelerators by using measured beam data. The uncertainty of such data sets limits for best achievable calculation accuracy. All these dosimetric measurements require good experience, are workful, take up resources needed for treatments and are prone to several random and systematic sources of errors. Appropriate verification of treatment location is more important in intensity modulated radiation therapy (IMRT) than in conventional RT. This is due to steep dose gradients produced within or close to healthy tissues locating only a few millimetres from the targeted volume. The thesis was concentrated in investigation of the quality of dosimetric measurements, the efficacy of dosimetric QC programs, the verification of measured beam data and the effect of positional errors on the dose received by the major salivary glands in head and neck IMRT. A method was developed for the estimation of the effect of the use of different dosimetric QC programs on the overall uncertainty of dose. Data were provided to facilitate the choice of a sufficient QC program. The method takes into account local output stability and reproducibility of the dosimetric QC measurements. A method based on the model fitting of the results of the QC measurements was proposed for the estimation of both of these factors. The reduction of random measurement errors and optimization of QC procedure were also investigated. A method and suggestions were presented for these purposes. The accuracy of beam data was evaluated in Finnish RT centres. Sufficient accuracy level was estimated for the beam data. A method based on the use of reference beam data was developed for the QC of beam data. Dosimetric and geometric accuracy requirements were evaluated for head and neck IMRT when function of the major salivary glands is intended to be spared. These criteria are based on the dose response obtained for the glands. Random measurement errors could be reduced enabling lowering of action levels and prolongation of measurement time interval from 1 month to even 6 months simultaneously maintaining dose accuracy. The combined effect of the proposed methods, suggestions and criteria was found to facilitate the avoidance of maximal dose errors of up to even about 8 %. In addition, their use may make the strictest recommended overall dose accuracy level of 3 % (1SD) achievable.Sädehoidossa annostarkkuus vaikuttaa ratkaisevasti hoidon onnistumisen todennäköisyyteen, eli kasvaimen häviämisen ja terveiden kudosten komplikaatioiden todennäköisyyksiin. Ulkoinen sädehoito toteutetaan nykyisin lähes aina lineaarikiihdyttimillä tuotetuilla tarkasti kohteen mukaisesti rajatuilla hoitokeiloilla. Merkittävimmin hoitoannoksen tarkkuuteen vaikuttaa annosmittausten tarkkuus, annosmittausten toteuttamisen määrittelevä laadunvarmistusohjelma, annoslaskennan tarkkuus ja hoidon geometrinen osuvuus. Työssä tarkasteltiin annostarkkuutta, sen parantamista ja laadunvarmistuksen optimointia ulkoisessa sädehoidossa. Tärkeimpänä tuloksena osoitettiin, että laadunvarmistukseen liittyvien työläiden annosmittausten määrä voidaan pudottaa jopa kuudesosaan säilyttäen optimaalinen annostarkkuus hyödynnettäessä työssä esitettyjä menetelmiä. Tulos helpottaa laadunvarmistukseen kuluvan sairaalafyysikoiden työmäärän optimointia ja maksimoi laiteajan käyttöä mittausten sijasta hoitoihin. Toisaalta samalla työmäärällä voidaan annostarkkuutta parantaa merkittävästi. Työ tuotti myös tuloksia ja menetelmiä, jotka helpottavat laadunvarmistuksen optimointia. Osoitettiin että on kannattavaa laskea mittausten toimenpiderajoja aina kun mittausten toistettavuus sen mahdollistaa. Annoslaskennassa tarvittavien mittaustietojen laadunvarmistusta varten tuotettiin tarkka referenssiaineisto. Näiden tietojen suhteen todettiin perustelluksi soveltaa hyvin tiukkoja tarkkuusvaatimuksia. Edellä mainituilla tekijöillä on vaikutusta kaikkien potilaiden saamiin hoitoannoksiin. Työssä esitetyt menetelmät todettiin helposti sovellettaviksi. Erityistapauksena arvioitiin tarkkuusvaatimukset suurten sylkirauhasten annoksille ja potilaan asettelulle kaulan alueen intensiteettimuokatussa sädehoidossa. Työn tulokset perustuivat pääasiassa kehitettyyn menetelmään, joka arvioi eri laadunvarmistusohjelmilla saavutettavan annostarkkuuden. Menetelmä huomioi annosmittausten epävarmuuden ja kiihdyttimen annostuoton epästabiilisuuden. Lisäksi kehitettiin mittaustulosten analyysimenetelmä, joka helpottaa satunnaisten mittausvirheiden havaitsemista mahdollistaen mittausten toimenpiderajojen laskemisen ja siten mittausvälin pidentämisen sekä jopa kiihdytinkohtaisten mittausvälien arvioimisen. Tämä osa työstä perustui HYKS:n syöpätautien klinikan 5 vuoden aikana keräämän laadunvarmistusaineiston analyysissä saatuihin havaintoihin ja tuloksiin. Annoslaskennan laadunvarmistusta varten työssä tarkasteltiin hyvin yleisesti käytössä olevien lineaarikiihdyttimien (Varian Clinac 600 ja 2100 CD) säteilykeilojen fysikaalisia ominaisuuksia. Näiden ominaisuuksien havaittu suuri yhdenmukaisuus mahdollisti tarkan referenssiaineiston muodostamisen. Aineiston tarkkuuden ja tarpeellisuuden varmistaminen tapahtui analysoimalla kaikissa Suomen sädehoitokeskuksissa tehtyjen annoslaskennan tarkistusmittausten tuloksia. Tarkkuusvaatimukset sylkirauhasten annoksille ja potilaan asettelulle perustuivat sylkirauhasille työssä määritettyyn annosvasteeseen ja annoksen muutokseen paikan suhteen näissä rauhasissa

Assessment of MRI-based Attenuation Correction for MRI-only Radiotherapy Treatment Planning of the Brain

Magnetic resonance imaging-only radiotherapy treatment planning (MRI-only RTP) and positron emission tomography (PET)-MRI imaging require generation of synthetic computed tomography (sCT) images from MRI images. In this study, initial dosimetric evaluation was performed for a previously developed MRI-based attenuation correction (MRAC) method for use in MRI-only RTP of the brain. MRAC-based sCT images were retrospectively generated from Dixon MR images of 20 patients who had previously received external beam radiation therapy (EBRT). Bone segmentation performance and Dice similarity coefficient of the sCT conversion method were evaluated for bone volumes on CT images. Dose calculation accuracy was assessed by recalculating the CT-based EBRT plans using the sCT images as the base attenuation data. Dose comparison was done for the sCT- and CT-based EBRT plans in planning target volume (PTV) and organs at risk (OAR). Parametric dose comparison showed mean relative differences of <0.4% for PTV and <1.0% for OARs. Mean gamma index pass rates of 95.7% with the 2%/2 mm agreement criterion and 96.5% with the 1%/1 mm agreement criterion were determined for glioma and metastasis patients, respectively. Based on the results, MRI-only RTP using sCT images generated from MRAC images can be a feasible alternative for radiotherapy of the brain.publishedVersionPeer reviewe

Diffusion-weighted magnetic resonance imaging for evaluation of salivary gland function in head and neck cancer patients treated with intensity-modulated radiotherapy

Background and purposes: Permanent xerostomia as a result of radiation-induced salivary gland damage remains a common side effect of radiotherapy (RT) of the head and neck. The purpose of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing the post-RT salivary gland function in patients with head and neck cancer (HNC). Materials and methods: In this prospective study, 20 HNC patients scheduled for bilateral neck chemoradiotherapy (CRT) with weekly cisplatin went through diffusion-weighted magnetic resonance imaging (DW-MRI) and salivary gland scintigraphy (SGS) prior to and at a mean of six months after completing the treatment. The changes in apparent diffusion coefficient (ADC) before and after treatment were compared with ejection fraction (EF) measured with SGS and the radiation dose absorbed by the salivary glands. Results: As a result of gustatory stimulation with ascorbic acid, the ADC showed a biphasic response with an initial increase and subsequent decrease. This pattern was seen both before and after RT. Post-RT ADC increased as a function of RT dose absorbed by the salivary glands. A moderate statistical correlation between pre- and post-RT ADCs at rest and EF measured with SGS was found. Conclusions: DW-MRI seems a promising tool for detection of physiological and functional changes in major salivary glands after RT. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Assessment of MRI-Based Attenuation Correction for MRI-Only Radiotherapy Treatment Planning of the Brain

Magnetic resonance imaging-only radiotherapy treatment planning (MRI-only RTP) and positron emission tomography (PET)-MRI imaging require generation of synthetic computed tomography (sCT) images from MRI images. In this study, initial dosimetric evaluation was performed for a previously developed MRI-based attenuation correction (MRAC) method for use in MRI-only RTP of the brain. MRAC-based sCT images were retrospectively generated from Dixon MR images of 20 patients who had previously received external beam radiation therapy (EBRT). Bone segmentation performance and Dice similarity coefficient of the sCT conversion method were evaluated for bone volumes on CT images. Dose calculation accuracy was assessed by recalculating the CT-based EBRT plans using the sCT images as the base attenuation data. Dose comparison was done for the sCT- and CT-based EBRT plans in planning target volume (PTV) and organs at risk (OAR). Parametric dose comparison showed mean relative differences of <0.4% for PTV and <1.0% for OARs. Mean gamma index pass rates of 95.7% with the 2%/2 mm agreement criterion and 96.5% with the 1%/1 mm agreement criterion were determined for glioma and metastasis patients, respectively. Based on the results, MRI-only RTP using sCT images generated from MRAC images can be a feasible alternative for radiotherapy of the brain

Acute Side-effects of Different Radiotherapy Treatment Schedules in Early Prostate Cancer

BACKGROUND: Optimal radiation therapy (RT) fractionation in early prostate cancer in elderly patients is controversial. We compared acute toxicities of fractionation schedules: 78/2 Gy, 60/3 Gy and 36.25/7.25 Gy, in this single-centre study. We also evaluated the effect of the rectal immobilization system Rectafix on quality of life (QoL). PATIENTS AND METHODS: Seventy-three patients with one or two intermediate prostate cancer risk factors according to National Comprehensive Cancer Network criteria were recruited. Twenty-one patients were treated with 78/2 Gy and 60/3 Gy, and 31 patients with 36.25/7.25 Gy. Their QoL data were assessed with regard to genitourinary, gastrointestinal and sexual wellbeing at the beginning and end of RT and at 3 months after treatment. Rectafix was used in the 78/2 Gy and 60/3 Gy groups. RESULTS: There were no statistically significant QoL differences in between the treatment groups 3 months after RT. The 78/2 Gy group had significantly increased bowel movements between baseline and 3 months after RT (p=0.036). At 3 months after RT, this group also had significantly more erectile dysfunction than the 60/3 Gy group (p=0.025). At the end of RT, the 78/2 Gy group had more symptoms than the 36.25/7.25 Gy group. Rectafix did not reduce acute toxicities in the 78/2 Gy or 60/3 Gy groups. CONCLUSION: Treatment with the 78/2 Gy schedule is no longer to be recommended due to its increased acute toxicity compared to treatments of 60/3 Gy and 36.25/7.25 Gy. The shortest schedule of 36.25 Gy in five fractions seems to be a convenient treatment option with tolerable acute toxicity.publishedVersionPeer reviewe

Measurement and properties of the dose-area product ratio in external small-beam radiotherapy

In small-beam radiation therapy (RT) the measurement of the beam quality parameter, i.e. the tissue-phantom ratio or TPR20,(10), using a conventional point detector is a challenge. To obtain reliable results, one has to consider potential sources of error, including volume averaging and adjustment of the point detector into the narrow beam. To overcome these challenges, a different type of beam quality parameter in small beams was studied, namely the dose-area product ratio, or DAPR(20),(10). With this method, the measurement of a dose-area product (DAP) using a large-area plane-parallel chamber (LAC) eliminates the uncertainties in detector positioning and volume averaging that are present when using a point detector. In this study, the properties of the DAPR(20),(10) of a cone-collimated 6 MV photon beam were investigated using Monte Carlo (MC) calculations and the obtained values were compared to measurements obtained using two LAC detectors, PTW Type 34073 and PTW Type 34070. In addition, the possibility of determining the DAP using EBT3 film and a Razor diode detector was studied. The determination of the DAPR(20),(10) value was found to be feasible in external small-beam radiotherapy using cone-collimated beams with diameters from 4-40 mm, based on the results of the two LACs, the MC calculations and the Razor diode. The measurements indicated a constant DAPR(20),(10) value for fields 20-40 mm in diameter, with a maximum relative change of 0.6%, but an increase of 7.0% for fields from 20-4 mm in diameter for the PTW Type 34070 chamber. Simulations and measurements showed an increase of DAPR(20),(10) with increasing LAC size or dose integral area for the studied 4-40 mm cone-collimated 6 MV photon beams. This has the consequence that there should be a reference to the size of the used LAC active area or the DAP integration area with the reported DAPR(20),(10) value

Dynamic Contrast-Enhanced Imaging as a Prognostic Tool in Early Diagnosis of Prostate Cancer : Correlation with PSA and Clinical Stage

Background and Purpose. Although several methods have been developed to predict the outcome of patients with prostate cancer, early diagnosis of individual patient remains challenging. The aim of the present study was to correlate tumor perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical prognostic factors and further to explore the diagnostic value of DCE-MRI parameters in early stage prostate cancer. Patients and Methods. Sixty-two newly diagnosed patients with histologically proven prostate adenocarcinoma were enrolled in our prospective study. Transrectal ultrasound-guided biopsy (12 cores, 6 on each lobe) was performed in each patient. Pathology was reviewed and graded according to the Gleason system. DCE-MRI was performed and analyzed using a two-compartmental model; quantitative parameters including volume transfer constant (Ktrans), reflux constant (Kep), and initial area under curve (iAUC) were calculated from the tumors and correlated with prostate-specific antigen (PSA), Gleason score, and clinical stage. Results. Ktrans (0.11 ± 0.02 min−1 versus 0.16 ± 0.06 min−1; p<0.05), Kep (0.38 ± 0.08 min−1 versus 0.60 ± 0.23 min−1; p<0.01), and iAUC (14.33 ± 2.66 mmoL/L/min versus 17.40 ± 5.97 mmoL/L/min; p<0.05) were all lower in the clinical stage T1c tumors (tumor number, n=11) than that of tumors in clinical stage T2 (n=58). Serum PSA correlated with both tumor Ktrans (r=0.304, p<0.05) and iAUC (r=0.258, p<0.05). Conclusions. Our study has confirmed that DCE-MRI is a promising biomarker that reflects the microcirculation of prostate cancer. DCE-MRI in combination with clinical prognostic factors may provide an effective new tool for the basis of early diagnosis and treatment decisions

Intensity-based dual model method for generation of synthetic CT images from standard T2-weighted MR images - Generalized technique for four different MR scanners

Background and purpose: Recent studies have shown that it is possible to conduct entire radiotherapy treatment planning (RTP) workflow using only MR images. This study aims to develop a generalized intensity-based method to generate synthetic CT (sCT) images from standard T2-weighted (T2(W)) MR images of the pelvis. Materials and methods: This study developed a generalized dual model HU conversion method to convert standard T2(W) MR image intensity values to synthetic HU values, separately inside and outside of atlas-segmented bone volume contour. The method was developed and evaluated with 20 and 35 prostate cancer patients, respectively. MR images with scanning sequences in clinical use were acquired with four different MR scanners of three vendors. Results: For the generated synthetic CT (sCT) images of the 35 prostate patients, the mean (and maximal) HU differences in soft and bony tissue volumes were 16 +/- 6 HUs (34 HUs) and -46 +/- 56 HUs (181 HUs), respectively, against the true CT images. The average of the PTV mean dose difference in sCTs compared to those in true CTs was -0.6 +/- 0.4% (-1.3%). Conclusions: The study provides a generalized method for sCT creation from standard T2(W) images of the pelvis. The method produced clinically acceptable dose calculation results for all the included scanners and MR sequences. (c) 2017 Elsevier B.V. All rights reserved.Peer reviewe