Therapy of chronic myeloid leukaemia can benefit from the activation of stem cells: simulation studies of different treatment combinations.

BACKGROUND: Newly diagnosed patients with chronic myeloid leukaemia (CML) are currently treated with tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib or dasatinib. However, incomplete eradication of residual disease is a general problem of long-term TKI therapy. Activation of mouse haematopoietic stem cells by interferon-α (IFNα) stimulated the discussion of whether a combination treatment leads to accelerated eradication of the CML clone. METHODS: We base our simulation approach on a mathematical model describing human CML as a competition phenomenon between normal and malignant cells. We amend this model to incorporate the description of IFNα activity and simulate different scenarios for potential treatment combinations. RESULTS: We demonstrate that the overall sensitivity of CML stem cells to IFNα activation is a crucial determinant for the benefit of a potential combination therapy. We furthermore show that pulsed IFNα together with continuous TKI administration is the most promising strategy for a combination treatment in which the therapeutic benefit prevails adverse side effects. CONCLUSION: Our modelling approach is a highly beneficial tool to quantitatively address the competition between normal and leukaemic haematopoiesis in treated CML patients. We derive testable predictions for different experimental settings that are suggested before the clinical implementation of the combination treatment.

Model-Based Selection for Proton Therapy in Breast Cancer: Development of the National Indication Protocol for Proton Therapy and First Clinical Experiences.

AIMS: Proton therapy is a radiation technique that yields less dose in normal tissues than photon therapy. In the Netherlands, proton therapy is reimbursed if the reduced dose to normal tissues is predicted to translate into a prespecified reduction in toxicity, based on nationally approved validated models. The aim of this paper is to present the development of a national indication protocol for proton therapy (NIPP) for model-based selection of breast cancer patients and to report on first clinical experiences. MATERIALS AND METHODS: A national proton therapy working group for breast cancer (PWG-BC) screened the literature for prognostic models able to estimate the individual risk of specific radiation-induced side-effects. After critical appraisal and selection of suitable models, a NIPP for breast cancer was written and subjected to comments by all stakeholders. The approved NIPP was subsequently introduced to select breast cancer patients who would benefit most from proton therapy. RESULTS: The model of Darby et al. (N Engl J Med 2013; 368:987-82) was the only model fulfilling the criteria prespecified by the PWG-BC. The model estimates the relative risk of an acute coronary event (ACE) based on the mean heart dose. The absolute lifetime risk of ACE <80 years was calculated by applying this model to the Dutch absolute incidence of ACE for female and male patients, between 40 and 70 years at breast cancer radiotherapy, with/without cardiovascular risk factors. The NIPP was approved for reimbursement in January 2019. Based on a threshold value of a 2% absolute lower risk on ACE for proton therapy compared with photons, 268 breast cancer patients have been treated in the Netherlands with proton therapy between February 2019 and January 2021. CONCLUSION: The NIPP includes a model that allows the estimation of the absolute risk on ACE <80 years based on mean heart dose. In the first 2 years, 268 breast cancer patients have been treated with proton therapy in The Netherlands.

A generic curriculum development model for the biomedical physics component of the educational and training programmes of the non-physics healthcare professions.

The objective of the study was the construction of a generic curriculum development model for the use of biomedical physics (BMP) educators teaching the non-physics healthcare professions (HCP) in Europe. A comprehensive, qualitative cross-sectional Europe-wide survey of the curricula delivered by BMP in Faculties of Medicine and Health Sciences (FMHS) was carried out. Curricular content was collected from faculty web-sites, curricular documents and textbooks. The survey data was supplemented with semi-structured interviews and direct observation during onsite visits. The number of faculties studied was 118 from 67 universities spread all over Europe, whilst the number of onsite visits/interviews was 15 (geographically distributed as follows: Eastern Europe 6, North Western Europe 5, and South Western Europe 4). EU legislation, recommendations by European national medical councils, educational benchmark statements by higher education quality assurance agencies, research journals concerning HCP education and other documents relevant to standards in clinical practice and undergraduate education were also analyzed. Best practices and BMP learning outcomes were elicited from the curricular materials, interviews and documentation and these were subsequently used to construct the curriculum development model. A structured, comprehensive BMP learning outcomes inventory was designed in the format required by the European Qualifications Framework (EQF). The structures of the inventory and curriculum development model make them ideally suited for use by BMP involved in European curriculum development initiatives for the HCP.

Multiresidue analysis of beta-agonists in bovine and porcine urine, feed and hair using liquid chromatography electrospray ionisation tandem mass spectrometry.

The use of beta-agonists as growth promoters in cattle breeding is forbidden in many countries for reasons of fair trade and consumer protection. In recent years the use of liquid chromatography (LC) tandem mass spectrometry (MS/MS) has been shown to be the method of choice for the control of beta-agonists. In this study an LC-MS/MS multiresidue analysis method is presented for trace analysis of 22 beta-agonists. A truly generic concept has been designed based on mixed-mode solid-phase extraction and positive electrospray ionisation LC-MS/MS operated in the multiple reaction monitoring mode. This method allows application to a wide variety of sample matrices such as urine, feed and hair, following minor modifications to the analysis procedure only. The method features fit-for-purpose sensitivity in urine as shown by CCalpha and CCbeta values of less than 0.2 and less than 0.5 microg/l respectively, for all beta-agonists studied (terbutaline and reproterol, less than 0.3 and less than 1.0 respectively). Similar but semiquantitative application to feed and hair showed CCbeta values of less than 10.0 and less than 5.0 microg/kg, respectively. A further simplification and improvement is demonstrated using Ultra Performance LC (UPLC) and fast-switching MS/MS. The successful validation of this method following the latest EU requirements and its application to real samples demonstrate that a new versatile tool has been achieved for veterinary control of beta-agonists.

UV radiation and cancer prevention: what is the evidence?

The health benefits of sunlight and the risk of skin cancer from UV exposure are still controversial. The literature was analyzed in terms of reviews, controlled and epidemiological studies for the relationships between sunshine exposure and overall cancer mortality, as well as mortality from cancer of the prostate, colon and breast. The residential and/or occupational sun exposure rate seemed to be positively correlated with a lower risk of overall morality due to organ cancer. A normal vitamin D status appeared to be an important precondition, via the local and autocrine synthesis of 1,25(OH)2D3 in the target tissues. The vitamin D hormone system is necessary for cell proliferation and differentiation; different types of vitamin D receptor gene polymorphism seemed to be associated with cancer cell growth. The health benefits of sunlight appear to outweigh the risk of skin cancer. However, the optimal UV exposure, the target level of circulating vitamin D, and whether vitamin D is the only pathway are still undetermined.

Role of interleukin 1 and granulocyte colony-stimulating factor in photofrin-based photodynamic therapy of rat rhabdomyosarcoma tumors.

Neutrophils play an important role in the efficacy of photodynamic therapy (PDT). These leukocytes rapidly accumulate into the tumor lesion after PDT and most likely eradicate the remaining attenuated tumor cells. The underlying mechanism of the accumulation of neutrophils at the time of PDT is not known. Therefore, we determined the effect of PDT on the course of mature and immature neutrophils in the circulation of rhabdomyosarcoma-bearing rats and studied the changes in the level of interleukin (IL)-1beta as an important stimulator of the proliferation of precursor cells of the granulocyte lineage in the bone marrow. We found that the effect of PDT on tumor growth was preceded by a rapid and specific increase of the number of mature neutrophils in the peripheral blood as early as 4 h after the start of PDT treatment and reaching maximum values after 8 h. At 24 h, the neutrophil numbers in the PDT-treated rats were still elevated as compared to sham-treated rats. In sham-treated rats, the numbers of blood monocytes and lymphocytes decreased by about 50% after 2 h and returned to their normal levels as soon as 2 h later. In PDT-treated rats, the course of monocyte numbers showed a similar pattern; however, lymphocyte numbers did not reach the normal range until 24 h. The specific increment of neutrophils was preceded by an increase of band neutrophil numbers and elevated serum levels of IL-1beta which were maximal at 2 h after the start of PDT. Pearson correlation analysis showed a significant association between the serum levels of IL-1beta at this time point and the number of band neutrophils at 4 h (R2 = 0.58; P = 0.03) and the number of mature neutrophils at 8 h (R2 = 0.54; P = 0.04). This suggests that PDT evoked an IL-1-dependent increased production rate of neutrophils in the bone marrow. Further investigation showed that the injection of anti-granulocyte colony-stimulating factor (G-CSF) antibodies not only attenuated the increase in neutrophil numbers but also greatly decreased the efficacy of PDT. On this basis, we suppose that an IL-1-induced release of G-CSF by PDT underlies this nonspecific immune reaction to the tumor. Apparently, G-CSF not only stimulates the production rate of neutrophils in the bone marrow but also increases the functional activity of these leukocytes to become indispensable tumor cell killers.

Evidence for an important role of neutrophils in the efficacy of photodynamic therapy in vivo.

To investigate the role of neutrophils in the efficacy of photodynamic therapy (PDT) in rhabdomyosarcoma-bearing rats, the number of these circulating phagocytes was decreased or increased before interstitial PDT by use of rabbit anti-rat neutrophil serum or granulocyte colony-stimulating factor, respectively. After administration of the antiserum, the number of circulating neutrophils decreased by 99.9%. However, the number of monocytes, lymphocytes, and platelets decreased as well (by 100%, 80%, and 25%, respectively). Under these conditions, PDT did not retard tumor growth at all. However, after cessation of the antiserum treatment 5 days after PDT, a striking decrease in the growth rate occurred subsequent to an increase above the normal range of the number of circulating neutrophils. Administration of the granulocyte colony-stimulating factor led to a specific 4-fold increase in the number of circulating neutrophils. In these rats, the tumor growth at day 2 after PDT was retarded as compared with PDT-treated rats that received saline only. Statistical evaluation of both experimental conditions showed that the efficacy of PDT, expressed as the percentage of change in tumor volume at day 2 after treatment, was dependent on the number of circulating neutrophils present at the day of PDT (P = 0.001; r2 = 0.482). Apparently, neutrophils are indispensable for successful PDT in vivo.

The influence of simultaneous integrated boost, hypofractionation and oncoplastic surgery on cosmetic outcome and PROMs after breast conserving therapy.

INTRODUCTION: We retrospectively investigated the possible influence of a simultaneous integrated boost (SIB), hypofractionation and oncoplastic surgery on cosmetic outcome in 125 patients with stage I-II breast cancer treated with breast conserving therapy (BCT). PATIENTS AND METHODS: The boost was given sequentially (55%) or by SIB (45%); fractionation was conventional (83%) or hypofractionated (17%); the surgical technique was a conventional lumpectomy (74%) or an oncoplastic technique (26%). We compared cosmetic results subjectively using a questionnaire independently completed by the patient and by the physician and objectively with the BCCT.core software. Independent-samples T-tests were used to compare outcome in different groups. Patients also completed the EORTC QLQ C30 and BR23. RESULTS: Univariate analyses indicated no significant differences of the cosmetic results (P ≤ 0.05) for the type of boost or fractionation. However, the conventional lumpectomy group scored significantly better than the oncoplastic group in the BCCT.core evaluation, without a significant difference in the subjective cosmetic evaluation. Quality of life outcome was in favour of SIB, hypofractionation and conventional surgery. CONCLUSION: Our study indicates that the current RT techniques seem to be safe for cosmetic outcome and quality of life. Further investigation is needed to verify the possible negative influence of oncoplastic surgery on the cosmetic outcome and the quality of life as this technique is especially indicated for patients with an unfavourable tumour/breast volume ratio.

Inhibition of cell proliferation by lithium is associated with interference in cdc2 activation.

Lithium can interfere with embryonal development in a variety of organisms. We investigated the effect of lithium on the proliferation of early embryonal cells. [3H]Thymidine incorporation of non-committed mouse P19 embryonal carcinoma cells was inhibited by lithium treatment. Similar effects were seen in a variety of other cells. This growth inhibition occurred in the G2 phase, since cells accumulated with a 4N DNA content, but the appearance of mitotic cells was blocked. Lithium could also prevent the activation of cdc2, thereby inhibiting cyclin B/cdc2 kinase activity. These data indicate that lithium might disturb embryonal development through interference in embryonal cell cycle regulation.

In vivo dosimetry during external photon beam radiotherapy.

In this critical review of the current practice of patient dose verification, we first demonstrate that a high accuracy (about 1-2%, 1 SD) can be obtained. Accurate in vivo dosimetry is possible if diodes and thermoluminescence dosimeters (TLDs), the main detector types in use for in vivo dosimetry, are carefully calibrated and the factors influencing their sensitivity are taken into account. Various methods and philosophies for applying patient dose verification are then evaluated: the measurement of each field for each fraction of each patient, a limited number of checks for all patients, or measurements of specific patient groups, for example, during total body irradiation (TBI) or conformal radiotherapy. The experience of a number of centers is then presented, providing information on the various types of errors detected by in vivo dosimetry, including their frequency and magnitude. From the results of recent studies it can be concluded that in centers having modern equipment with verification systems as well as comprehensive quality assurance (QA) programs, a systematic error larger than 5% in dose delivery is still present for 0.5-1% of the patient treatments. In other studies, a frequency of 3-10% of errors was observed for specific patient groups or when no verification system was present at the accelerator. These results were balanced against the additional manpower and other resources required for such a QA program. It could be concluded that patient dose verification should be an essential part of a QA program in a radiotherapy department, and plays a complementary role to treatment-sheet double checking. As the radiotherapy community makes the transition from the conventional two-dimensional (2D) to three-dimensional (3D) conformal and intensity modulated dose delivery, it is recommended that new treatment techniques be checked systematically for a few patients, and to perform in vivo dosimetry a few times for each patient for situations where errors in dose delivery should be minimized.

Transmission dosimetry with a liquid-filled electronic portal imaging device.

PURPOSE: To assess the accuracy of transmission dose rate measurements for various phantom-detector geometries, performed with an electronic portal imaging device (EPID) and to compare these transmission dose rate values with exit dose rate data. METHODS AND MATERIALS: Transmission dose rate values on the central beam axis and beam profiles were measured with an EPID consisting of a matrix of liquid-filled ionization chambers. These data were compared with transmission and exit dose rate values, obtained using air-filled ionization chambers for a number of field sizes, phantom thickness, and phantom-detector distances. Various homogeneous and inhomogeneous phantoms were applied. RESULTS: The increase in dose rate with field size is larger for the EPID than in air, due to the larger amount of side scatter in the EPID. The difference has been taken into account by a deconvolution of the EPID images. An additional build-up layer on top of the commercial device is needed to reach dose maximum at the liquid ionization chambers for photon beam energies higher than about 4 MV. The transmission off-axis ratios (OAR) determined with the EPID and in air agreed within 2% for all tested cases, after deconvolution of the EPID signal. The agreement between the EPID-and exit-OAR decreased with increasing phantom-detector distance and the presence of inhomogeneities. For a phantom-detector distance of about 10 cm, the EPID- and exit-OARs agree within 2.5%. The difference could be up to 8% for an air inhomogeneity and a phantom-detector distance of 30 cm. CONCLUSIONS: The difference between EPID measurements and measurements in air can be explained by side scatter effects in the EPID and lack of adequate buildup, and can easily be taken into account. The loss of scatter compared with the situation at the exit side of the phantom explains the difference between transmission and exit dose values. At short phantom-detector distances, good agreement exists between transmission and exit dose rate. This implies that at this distance, the EPID can be used for simple comparison with exit dose calculations during patient treatments. At larger distances, more sophisticated conversion methods are required.

New method to obtain the midplane dose using portal in vivo dosimetry.

PURPOSE: The aim of this study was to develop a method to derive the midplane dose [i.e., the two-dimensional (2D) dose distribution in the middle of a patient irradiated with high-energy photon beams] from transmission dose data measured with an electronic portal imaging device (EPID). A prerequisite for this method was that it could be used without additional patient information (i.e., independent of a treatment-planning system). Second, we compared the new method with several existing (conventional) methods that derive the midline dose from entrance and exit dose measurements. METHODS AND MATERIALS: The proposed method first calculates the 2D contribution of the primary and scattered dose component at the exit side of the patient or phantom from the measured transmission dose. Then, a correction is applied for the difference in contribution for both dose components between exit side and midplane, yielding the midplane dose. To test the method, we performed EPID transmission dose measurements and entrance, midplane, and exit dose measurements using an ionization chamber in homogeneous and symmetrical inhomogeneous phantoms. The various methods to derive the midplane dose were also tested for asymmetrical inhomogeneous phantoms applying two opposing fields. A number of combinations of inhomogeneities (air, cork, and aluminum), phantom thicknesses, field sizes, and a few irregularly shaped fields were investigated, while each experiment was performed in 4-, 8-, and 18-MV open and wedged beams. RESULTS: Our new method can be used to assess the midplane dose for most clinical situations within 2% relative to ionization chamber measurements. Similar results were found with other methods. In the presence of large asymmetrical inhomogeneities (e.g., lungs), discrepancies of about 8% have been found (for small field sizes) using our transmission dose method, owing to the absence of lateral electron equilibrium. Applying the other methods, differences between predicted and measured midplane doses were even larger, up to 10%. For large field sizes, the agreement between measured and predicted midplane dose was within 3% using our transmission dose method. CONCLUSIONS: Using our new method, midplane doses were estimated with a similar or higher accuracy compared with existing conventional methods for in vivo dosimetry. The advantage of our new method is that the midplane dose can be determined in the entire (2D) field. With our method, portal in vivo dosimetry is an accurate alternative for conventional in vivo dosimetry.

Chest wall irradiation with MLC-shaped photon and electron fields.

PURPOSE: To improve the treatment technique for chest wall irradiation, using the multileaf collimator (MLC) of the MM50 Racetrack Microtron to shape both photon and electron beams, and to check the dose delivery in the match-line region of these fields for the routine and improved technique. METHODS AND MATERIALS: Using diode and film phantom measurements, the optimal number of photon beam segments and their positions relative to the electron beam were determined. On phantoms, and during actual patient treatment using in vivo dosimetry, the dose homogeneity in the match-line region was determined for both the routine and improved techniques. RESULTS: Three photon beam segments (9-mm gap, perfect match, and 9-mm overlap) were used to match the electron beam, resulting in minimum-maximum dose values in the match-line region of 88-109%, compared to 80-115% for the routine technique (2 photon beam segments). During patient treatment, the average minimum and maximum dose values were 95% and 115%, respectively, compared to 78% and 127%, respectively, for the routine technique. The interfraction variation in dose delivery was reduced from 11.0% (1 SD) to 4.6% (1 SD). The actual treatment time was reduced from 10 to 4.5 min. CONCLUSION: Using the MLC of the MM50 to shape both photon and electron beams, an improved treatment technique for chest wall irradiation was developed, which is less labor intensive, faster, and yields a more homogeneous, and better reproducible dose delivery.

Dosimetric characteristics of a liquid-filled electronic portal imaging device.

PURPOSE: To determine the characteristics of a commercial electronic portal imaging device (EPID), based on a two-dimensional matrix of liquid-filled ionization chambers, for transmission dose measurements during patient treatment. METHODS AND MATERIALS: Electronic portal imaging device measurements were performed in a cobalt-60 beam and two accelerator x-ray beams, and compared with measurements performed with a Farmer-type ionization chamber in air in a miniphantom and in an extended water phantom. RESULTS: The warming up time of the EPID is about 1 h. The long-term stability of the detector is better than 1% under reference conditions for a period of about 3 months. The signal of the ionization chambers follows approximately the square root of the dose rate, although the relation becomes more linear for larger (> 1 Gy/min) dose rates. The signal can be transformed to dose rate with an accuracy of 0.6% (1 SD). The short-term influence of integrated dose on the sensitivity of the ionization chambers is small. The sensitivity increases about 0.5% for all ionization chambers after an absorbed dose of 8 Gy and returns to its original value in less than 5 min after stopping the irradiation. This small increase in sensitivity can be ascribed to the electrode distance of the ionization chambers in commercial EPIDs, which is 0.8 +/- 0.1 mm. The sensitivity increase depends on the electrode distance and is 4% for a 1.4 mm electrode distance. The scattering properties of the EPID ionization chambers were between those of an ionization chamber in a miniphantom and in a water phantom. CONCLUSION: The matrix ionization chamber EPID has characteristics that make it very suitable for dose rate measurements. It is therefore a very promising device for in vivo dosimetry purposes.

Beam intensity modulation for penumbra enhancement in the treatment of lung cancer.

PURPOSE: A treatment planning study was performed for patients with lung cancer in order to investigate the extent to which doses to critical structures could be reduced by penumbra enhancement at the superior and inferior field edges, using beam intensity modulation (BIM) with a multileaf collimator. By applying two independent published models for the prediction of the incidence of normal tissue complications, the potential for dose escalation without increasing the incidence of pneumonitis was estimated. METHODS AND MATERIALS: For 12 patients, the standard treatment technique was compared with the BIM technique using the Cadplan 3D planning system (Varian-Dosetek). Dose distributions in the healthy lung tissue were evaluated by considering both lungs minus the tumor as one functional unit. The following parameters were compared: (i) the average normalized total dose (NTD), (ii) the lung volume receiving an NTD of more than 20 Gy, and (iii) the calculated normal tissue complication probability (NTCP). RESULTS: Due to the applied BIM technique, the field lengths could be reduced by 1.4 cm for all patients, while achieving a minimum dose at the superior and inferior parts of the target of 95% of the isocenter dose. Compared to the standard technique, BIM reduced the patient mean of the average NTD for the healthy lung tissue from 16.5 to 15.3 Gy. The volume of healthy lung tissue receiving an NTD of 20 Gy or more was reduced by 9.7% (range 2.2 to 23.1%). The calculated NTCP reduced from 10.7% to 7.6% on average. The length of the esophagus that received a dose of 60 Gy or more could be reduced for 5 of the 6 stage III patients in this study. Based on equal lung NTCPs for the standard technique and the BIM technique, a mean dose escalation of 5.7 Gy (range 1.1 to 16.0 Gy) was possible for the 12 patients in this study. Based on equal average NTDs for the two techniques, the patient mean of the allowed dose escalation was 6.5 Gy (range 1.1 to 18.2 Gy). All dose escalations would be possible without exceeding the spinal cord tolerance dose. CONCLUSIONS: The BIM technique reduced the dose delivery to critical tissues. Two published methods for estimating the incidence of pneumonitis both pointed to a potential for dose escalation of 6 to 7 Gy on average with the BIM technique, without increasing the incidence of pneumonitis. For 2 of the 12 patients in this study the estimated allowed dose escalation even exceeded 15 Gy.

An analysis of anatomic landmark mobility and setup deviations in radiotherapy for lung cancer.

PURPOSE: To identify thoracic structures that exhibit little internal motion during irradiation and to determine setup variations in patients with lung cancer. METHODS AND MATERIALS: Intrafractional images were generated with an electronic portal-imaging device from the AP fields of 10 patients, during several fractions. To determine the intrafractional mobility of thoracic structures, visible structures were contoured in every image and matched with a reference image by means of a cross-correlation algorithm. Setup variations were determined by comparing portal images with the digitized simulator films using the stable structures as landmarks. RESULTS: Mobility was limited in the lateral direction for the trachea, thoracic wall, paraspinal line, and aortic notch, and in the craniocaudal direction for the clavicle, aortic notch, and thoracic.wall. Analysis of patient setup revealed random deviations of 2.0 mm (1 SD) in the lateral direction and 2.8 mm in the craniocaudal direction, while the systematic deviations were 2.5 and 2.0 mm (1 SD) respectively. CONCLUSIONS: We have identified thoracic structures that exhibit little internal motion in the frontal plane, and recommend that these structures be used for verifying patient setup during radiotherapy. The daily variation in the setup of lung cancer patients at our center appears to be acceptable.

In vivo dosimetry during conformal therapy of prostatic cancer.

In vivo dose measurements were performed during the simultaneous boost technique for prostatic cancer to check the accuracy of dose calculations by a monitor unit calculation program and a three-dimensional planning system. The dose of the large field and the boost field are given simultaneously using customized 10 mm thick Roses-metal blocks in which the boost field is cut out. Following the procedure of the quality assurance protocol for this technique, the dose at the specification point has been determined by in vivo dosimetry. The measured dose was initially too high for 5 out of 16 patients, due to unexpected differences in two beams with the same nominal beam quality and a different density correction for the femoral heads; the monitor unit calculation program was therefore checked and improved. The dose at the specification point was also compared with calculations performed by a CT-based three-dimensional (3-D) planning system. The average deviation of the 3-D planning system from the measurements is 0.1% +/- 1.2%. Entrance, midline and exit dose values in the central axial plane, in a cranial plane and in a plane under the transmission block have also been compared with calculations performed by the 3-D treatment planning system. The measured entrance dose is, on average, 3.4% higher than the calculated dose for the AP beam and up to 5.5% for the lateral beams. Phantom measurements were performed and showed that these differences were not related to patient set-up errors.(ABSTRACT TRUNCATED AT 250 WORDS)

A linear diode array (JFD-5) for match line in vivo dosimetry in photon and electron beams; evaluation for a chest wall irradiation technique.

BACKGROUND AND PURPOSE: In vivo dosimetry using thermoluminiscence detectors (TLD) is routinely performed in our institution to determine dose inhomogeneities in the match line region during chest wall irradiation. However, TLDs have some drawbacks: online in vivo dosimetry cannot be performed; generally, doses delivered by the contributing fields are not measured separately; measurement analysis is time consuming. To overcome these problems, the Joined Field Detector (JFD-5), a detector for match line in vivo dosimetry based on diodes, has been developed. This detector and its characteristics are presented. MATERIALS AND METHODS: The JFD-5 is a linear array of 5 p-type diodes. The middle three diodes, used to measure the dose in the match line region, are positioned at 5-mm intervals. The outer two diodes, positioned at 3-cm distance from the central diode, are used to measure the dose in the two contributing fields. For three JFD-5 detectors, calibration factors for different energies, and sensitivity correction factors for non-standard field sizes, patient skin temperature, and oblique incidence have been determined. The accuracy of penumbra and match line dose measurements has been determined in phantom studies and in vivo. RESULTS: Calibration factors differ significantly between diodes and between photon and electron beams. However, conversion factors between energies can be applied. The correction factor for temperature is 0.35%/ degrees C, and for oblique incidence 2% at maximum. The penumbra measured with the JFD-5 agrees well with film and linear diode array measurements. JFD-5 in vivo match line dosimetry reproducibility was 2.0% (1 SD) while the agreement with TLD was 0.999+/-0.023 (1 SD). CONCLUSION: The JFD-5 can be used for accurate, reproducible, and fast on-line match line in vivo dosimetry.

Dosimetric control of conformal treatment of parotid gland tumours.

The purpose of this study was to determine the dosimetric accuracy of the treatment of parotid gland tumours using 8 MV X-ray beams. These tumours are generally situated near the patient's skin. Entrance in vivo dose measurements with diodes were obtained for 20 patients during 5 sessions per patient, in the anterior-oblique and posterior-oblique wedged fields, on the central beam axis as well as in points situated in a cranial plane 2 or 3 cm off-axis. Phantom measurements were performed in order to determine the actual position of the 95% isodose surface. The measurements were compared with calculations performed with our three-dimensional treatment planning system. The reproducibility of the diode measurements on patients was found to be 1.4% (1 SD). The total accuracy in the entrance dose determination for the average of 2 measurements was 1.8% (1 SD). The central axis entrance dose for the anterior field was on average 1.5% +/- 3.2% (1 SD) higher than the calculated value. For the posterior field, the difference was 0.9% +/- 3.1% (1 SD). The deviations for the off-axis points were somewhat smaller, mainly due to overestimation of the block effect in the calculations. The value of the dose at the isocentre obtained by extrapolation of the measured entrance dose values, differed 0.3% +/- 2.1% from the calculations. The accuracy in dose determination at the isocentre was 2% (1 SD). After correction for the difference in prescribed and actual source-to-skin distance, the results showed good agreement with phantom measurements on a polystyrene phantom without inhomogeneities, performed both with diodes and an ionization chamber.(ABSTRACT TRUNCATED AT 250 WORDS)

Commissioning of a commercially available system for intensity-modulated radiotherapy dose delivery with dynamic multileaf collimation.

PURPOSE: To commission commercially available equipment for intensity-modulated radiotherapy (IMRT) using dynamic multileaf collimation (DMLC). MATERIALS AND METHODS: First, the stability in leaf positioning and in realized IMRT profiles on a Varian 2300 C/D machine were determined as a function of time and gantry angle, and as a result of treatment interrupts. Second, dose distributions calculated with the CadPlan (Varian) treatment planning system, using leaf trajectories calculated with the leaf motion calculator (LMC) algorithm, were compared with distributions realized at the 2300 C/D unit. RESULTS: Day-to-day and gantry angle variations in leaf positioning and dose delivery were very small (less than 0.1-0.2 mm and 2%). The effect of treatment interrupts on measured dose distributions was less than 2%. The agreement between the final dose distribution calculated by CadPlan and the measured dose was generally within 2%, or 2 mm at steep dose gradients, using a leaf transmission value of 1.8% and a leaf separation value of 2 mm in LMC. For narrow peaks, deviations of up to 6% were observed. LMC does not synchronize adjacent leaf trajectories resulting in tongue-and-groove underdosages of up to 29% for extreme cases. CONCLUSIONS: The 2300 C/D machine is suitable for accurate and reproducible DMLC treatments. The agreement between dose predictions with LMC and CadPlan, and realized doses at this unit is clinically acceptable for most cases. However, differences between calculated and actual dose values may exist in peaked fluences or due to tongue-and-groove effects. Therefore, pretreatment dosimetric verification for each patient is recommended.