Associations between tumor vascularization assessed by in vivo DCE-MRI and the presence of disseminated tumor cells in bone marrow in breast cancer patients at the time of diagnosis.

PURPOSE: To explore possible associations between in vivo pharmacokinetic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and the presence of disseminated tumor cells (DTCs) in bone marrow in breast cancer patients at the time of diagnosis. MATERIALS AND METHODS: Thirty-seven women with breast cancer (stage T2-4N0-1M0) were included. Patients were classified as DTC+ if one or more DTCs were detected by immunocytochemistry. DCE-MRI was acquired with a radial 3D T1 -weighted spoiled gradient echo sequence with k-space weighted image contrast. K(trans), kep, and ve were calculated using the extended Tofts model and a population-derived arterial input function. The nonparametric Mann-Whitney U-test was used to compare the histogram distributions of the pharmacokinetic parameters for the DTC+ and the DTC- patients. RESULTS: DTCs were detected in 7 of the 37 patients (19%). In DTC+ patients, the distribution of tumor K(trans) and kep were significantly (P < 0.01) more shifted towards lower values than in DTC- patients. CONCLUSION: An association between vascular dependent pharmacokinetic DCE-MRI parameters and the presence of DTCs were found. Compared to DTC- patients, DTC+ patients had poorer perfusion and permeability, indicative of hypoxia. Thus, pharmacokinetic parameters might be surrogate biomarkers of metastatic potential and future relapse.

Routine pelvic MRI using phased-array coil for detection of extraprostatic tumour extension: accuracy and clinical significance.

OBJECTIVES: To determine the accuracy and assess the clinical significance of surface-coil 1.5-T magnetic resonance imaging (MRI) for the detection of locally advanced prostate cancer (PCa). METHODS: Between December 2007 and January 2010, we examined 209 PCa patients (mean age = 62.5 years) who were consecutively treated with robot-assisted laparoscopic prostatectomy and prospectively staged by MRI. One hundred and thirty-five patients (64.6 %) had locally advanced disease. Conventional clinical tumour stage and MRI-assessed tumour stage were compared with histopathological tumour stage (pT). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy (OA) were calculated using pT as the "gold standard". Overstaged and understaged cases at MRI were reviewed. RESULTS: Sensitivity, specificity, PPV, NPV and OA for the detection of locally advanced disease were 25.9, 95.9, 92.1, 41.2 and 50.5 % and 56.3, 82.2, 85.4, 50.4 and 65.4 % for clinical staging and MRI, respectively. Among patients understaged at MRI, the resection margins were free in 64.4 % of the cases (38/59). CONCLUSIONS: Although the accuracy was limited, the detection of locally advanced disease improved substantially when MRI was added to routine clinical staging. The majority of the understaged patients nevertheless achieved free margins. When assessing the clinical significance of MRI staging the extent of extraprostatic extension has to be considered.

Assessment of liposome biodistribution by non-invasive optical imaging: a feasibility study in tumour-bearing mice.

Liposomal encapsulation of cytostatics improves drug delivery to tumour tissue and reduces dose-limiting systemic toxicities. Development and evaluation of new liposome formulations is time consuming and costly with high demands for experimental animals. A faster and less demanding means of comparing several product candidates may be provided by use of non-invasive methods for assessing pharmacokinetics and biodistribution. In this study we have evaluated the feasibility of using small animal fluorescence optical imaging as a strategy to study liposome accumulation in tumours. Liposomal doxorubicin (Caelyx) was labelled with a lipophilic carbocyanine tracer and administered to tumour-bearing mice. Subsequently, the in vivo distribution of the labelled liposomes was followed over time by fluorescent optical imaging. The results revealed a gradual increase in tumour fluorescence, indicating accumulation of the liposomes reaching plateau levels at 48 h post injection. However, due to loss of dye from liposomes during circulation combined with substantial scattering and absorption of in vivo fluorescent signal, reliable quantitative correlation between the biodistribution profile of the labelled liposomes and doxorubicin could not be obtained.

Dose evaluation and risk estimation for secondary cancer in contralateral breast and a study of correlation between thorax shape and dose to organs at risk following tangentially breast irradiation during deep inspiration breath-hold and free breathing.

PURPOSE: To assess the impact of using breathing adapted radiotherapy on contralateral breast (CB) dose, to relate the thorax shape with the dose to the organs at risk (OARs) and to predict the risk for induced malignancies in CB using linear and non-linear models, following tangential irradiation of breast. MATERIAL AND METHODS: Sixteen patients with stage I-II breast cancer treatment planned with tangential fields using deep inspiration breath hold (DIBH) and free breathing (FB) techniques were included in this analysis. The dose results mainly based on DVH analysis were compared. Four parameters were defined to describe thoracic shape. Excess relative risk (ERR) for cancer induction in CB, employing linear and non-linear models was calculated. RESULTS: Average CB volumes exposed to a dose of 1 Gy is 1.3 times higher in DIBH plans than in FB plans. No significant difference in average V3Gy and V5Gy for DIBH and FB plans is observed. The average mean CB dose for DIBH and FB plans is 0.33 and 0.28 Gy, respectively. No correlation between thorax shape parameters and mean OARs dose is observed. The estimated average mean ERR with linear model is lower in FB plans (0.12) than for the DIBH plans (0.14). The estimated ERR with non-linear model is 0.14 for DIBH plans and 0.15 for FB plans. CONCLUSION: No significant difference in CB dose between DIBH and FB plans is observed. The four thorax shape parameters defined in this study can not be related to the dose at OARs using DIBH and FB radiation techniques. The ERR estimates for secondary CB cancer are nearly the same for FB and DIBH planning when using a linear and non-linear risk prediction models.

Diffusion-weighted magnetic resonance imaging for pretreatment prediction and monitoring of treatment response of patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy.

BACKGROUND: For patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy (NACT), the European Guidelines for Breast Imaging recommends magnetic resonance imaging (MRI) to be performed before start of NACT, when half of the NACT has been administered and prior to surgery. This is the first study addressing the value of flow-insensitive apparent diffusion coefficients (ADCs) obtained from diffusion-weighted (DW) MRI at the recommended time points for pretreatment prediction and monitoring of treatment response. MATERIALS AND METHODS: Twenty-five LABC patients were included in this prospective study. DW MRI was performed using single-shot spin-echo echo-planar imaging with b-values of 100, 250 and 800 s/mm(2) prior to NACT, after four cycles of NACT and at the conclusion of therapy using a 1.5 T MR scanner. ADC in the breast tumor was calculated from each assessment. The strength of correlation between pretreatment ADC, ADC changes and tumor volume changes were examined using Spearman's rho correlation test. RESULTS: Mean pretreatment ADC was 1.11 + or - 0.21 x 10(-3) mm(2)/s. After 4 cycles of NACT, ADC was significantly increased (1.39 + or - 0.36 x 10(-3) mm(2)/s; p=0.018). There was no correlation between individual pretreatment breast tumor ADC and MR response measured after four cycles of NACT (p=0.816) or prior to surgery (p=0.620). CONCLUSION: Pretreatment tumor ADC does not predict treatment response for patients with LABC undergoing NACT. Furthermore, ADC increase observed mid-way in the course of NACT does not correlate with tumor volume changes.

Improved image quality of low-dose thoracic CT examinations with a new postprocessing software.

In 2008 a phantom study indicated that there is a potential for reducing the CT doses when using a new postprocessing filter. The purpose of this study was to test this new postprocessing filter clinically for low-dose chest CT examinations, to assess whether the diagnostic performance is the same or improved. A standardized clinical chest CT protocol was used on patients with colorectal cancer. Only mA settings changed between patients according to patient size. One standard and one low-dose chest protocol were performed for all patients. The low-dose images were postprocessed with a new software filter, which provides context-controlled restoration of digital images by using adaptive filters. Three radiologists assessed randomly all the images independently. A total of 24 scan series were evaluated with respect to image quality according to quality criteria from the European guidelines for chest CT using a five-point scale; 576 details were assessed. Overall mean score is the average score for all details rated for all three readers for all full-dose series, low-dose series and low-dose enhanced series, respectively. The statistical methods used for comparison were paired sampled t-test and intraclass correlation coefficient. The postprocessing filter improved the diagnostic performance compared to the unenhanced low-dose images. Mean score for full-dose, low-dose and low-dose enhanced series were 3.8, 3.0 and 3.3, respectively. For all patients the full-dose series gave higher scores than the low-dose series. Intraclass correlation coefficients were 0.2, 0.1 and 0.3 for the full-dose, low-dose and low-dose enhanced series, respectively. There is a potential for improving diagnostic performance of low-dose CT chest examinations using this new postprocessing filter.

Late regional density changes of the lung after radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: To investigate density changes in lung tissue, 3-4 years after postoperative adjuvant radiotherapy for breast cancer, based on dose dependence and regional differences. MATERIAL AND METHODS: Sixty-one breast cancer patients, who had received computed tomography (CT) based postoperative radiotherapy, were included. CT scans were performed 35-51 months after start of radiotherapy. Dose information and CT scans from before and after radiotherapy were geometrically aligned in order to analyse changes in air-filled fraction (derived from CT density) as a function of dose for different regions of the lung. RESULTS: Dose-dependent reduction of the air-filled fraction was shown to vary between the different regions of the lung. For lung tissue receiving about 50 Gy, the largest reduction in air-filled fraction was found in the cranial part of the lung. An increased air-filled fraction was observed for lung tissue irradiated to doses below 20 Gy, indicating compensatory response. CONCLUSIONS: The treatment-induced change in whole-lung density is a weighted response, involving the different regions, the irradiated volumes, and dose levels to these volumes. Simplistic models may therefore not be appropriate for describing the whole-lung dose-volume-response relationship following inhomogeneous irradiation.

The elimination of low-dose hyper-radiosensitivity by transfer of irradiated-cell conditioned medium depends on dose rate.

Irradiation of T-47D cells with 0.3 Gy delivered by a (60)Co source at a low dose rate of 0.3 Gy/h abolished low-dose hyper-radiosensitivity (HRS) for at least 14 months (with continuous cell culturing), while the same dose administered acutely (40 Gy/h) eliminated HRS for less than 24 h. Medium transferred from the low-dose-rate primed cells (low-dose-rate ICCM) to unirradiated cells eliminated HRS in recipient cells even if the donor cells had been cultivated for 14 months after the priming dose. Thus low-dose-rate priming activates mechanisms that involve modification or induction of a factor in the medium. This factor affects unirradiated cells in such a way that HRS is eliminated in cells exposed to medium from the primed cells. However, only cells directly exposed to low-dose-rate radiation induce or modify the putative factor, since unirradiated cells that were exposed to low-dose-rate ICCM regained HRS within 2 weeks of cultivation in fresh medium. The ability of ICCM to eliminate HRS in recipient cells is dependent on dose rate. However, an increase in clonogenic survival was observed in cells receiving only medium transfer without subsequent irradiation that was independent of dose rate.

A planning comparison of dose patterns in organs at risk and predicted risk for radiation induced malignancy in the contralateral breast following radiation therapy of primary breast using conventional, IMRT and volumetric modulated arc treatment techniques.

PURPOSE: To investigate the impact of using different radiation therapy techniques on contra-lateral breast (CB) dose, and also dose to other involved organs at risk such as heart and lungs following radiation therapy of breast and regional lymph nodes. Furthermore, to predict the risk for induced malignancies in CB using linear and non linear models. MATERIAL AND METHODS: Eight patients with stage II-III breast cancer were included in this analysis. It was focused on three treatment techniques; conventional radiotherapy technique forwardly planed, IMRT and volumetric modulated arc (RapidArc) techniques, inversely planed. The CC algorithm was employed to calculate the standard treatment plans whereas for the IMRT and RapidArc treatment plans AAA algorithm was adopted. The dose results based on mostly DVH analysis were compared. The excess relative risk (ERR) for cancer induction in CB, employed both linear and non-linear models, was estimated. RESULTS: A better homogeneity and conformation in PTV was observed in the RapidArc plans. The highest minimum dose to PTV was observed in the conventional plans while no difference was observed for minimum significant doses D(98%) and D(99%) where D(X%) is the dose received by X% of the PTV volume. In terms of organ sparing, the IMRT and RapidArc plans spare ipsilateral-lung better, but a 40% lower mean dose in the contra-lateral lung in the conventional plans is observed. The mean dose to the contra-lateral breast was lowest for the RapidArc plans as well as the V(10Gy) and the maximum dose. The mean predicted ERR for the eight patients were lower for the conventional and RA plans than for the IMRT plans assuming a linear dose-risk relationship. The mean predicted ERR when using a non linear model was lower for all the three techniques (with lowest ERR for RapidArc plans). CONCLUSIONS: From a clinical perspective, it should be concluded that all three solutions investigated in the study can offer high quality treatment of patients. Further comparative analysis of the two algorithms used in the present study, however, should be performed especially on the peripheral organ dose. The impact of CB exposure to a low-dose radiation on minimizing the risk of radiation induced malignancy in CB can be interpreted differently when using linear or non linear models to predict ERR. In general, no detriment was observed when using RapidArc compared to conventional treatments while a potentially higher risk could be associated to IMRT treatments with fixed gantry.

Principal component analysis for the comparison of metabolic profiles from human rectal cancer biopsies and colorectal xenografts using high-resolution magic angle spinning 1H magnetic resonance spectroscopy.

BACKGROUND: This study was conducted in order to elucidate metabolic differences between human rectal cancer biopsies and colorectal HT29, HCT116 and SW620 xenografts by using high-resolution magnetic angle spinning (MAS) magnetic resonance spectroscopy (MRS) and for determination of the most appropriate human rectal xenograft model for preclinical MR spectroscopy studies. A further aim was to investigate metabolic changes following irradiation of HT29 xenografts. METHODS: HR MAS MRS of tissue samples from xenografts and rectal biopsies were obtained with a Bruker Avance DRX600 spectrometer and analyzed using principal component analysis (PCA) and partial least square (PLS) regression analysis. RESULTS AND CONCLUSION: HR MAS MRS enabled assignment of 27 metabolites. Score plots from PCA of spin-echo and single-pulse spectra revealed separate clusters of the different xenografts and rectal biopsies, reflecting underlying differences in metabolite composition. The loading profile indicated that clustering was mainly based on differences in relative amounts of lipids, lactate and choline-containing compounds, with HT29 exhibiting the metabolic profile most similar to human rectal cancers tissue. Due to high necrotic fractions in the HT29 xenografts, radiation-induced changes were not detected when comparing spectra from untreated and irradiated HT29 xenografts. However, PLS calibration relating spectral data to the necrotic fraction revealed a significant correlation, indicating that necrotic fraction can be assessed from the MR spectra.

Estimated risk for secondary cancer in the contra-lateral breast following radiation therapy of breast cancer.

PURPOSE: To facilitate a discussion about the impact of dose heterogeneity on the risk for secondary contralateral breast (CB) cancer predicted with linear and non linear models associated with primary breast irradiation. METHODS AND MATERIALS: Dose volume statistics of the CB calculated for eight patients using a collapsed cone algorithm were used to predict the excess relative risk (ERR) for cancer induction in CB. Both linear and non-linear models were employed. A sensitivity analysis demonstrating the impact of different parameter values on calculated ERR for the eight patients was also included in this study. RESULTS: A proportionality assumption was established to make the calculations with a linear and non-linear model comparable. ERR of secondary cancer predicted by the linear model varied considerably between the patients, while the predicted ERR for the same patients using the non-linear model showed very small variation. The predicted ERRs by the two models were indistinguishable for small doses, i.e. below approximately 3 Gy. The sensitivity analysis showed that the quadratic component of the radiation-induction pre-malignant cell term is negligible for lower dose level. The ERR is highly sensitive to the value of alpha(1) and alpha(2). CONCLUSIONS: Optimization of breast cancer radiation therapy, where also the risk for radiation induced secondary malignancies in the contralateral breast is taken into account, requires robust and valid risk assessment. The linear dose-risk model does not account for the complexity in the mechanisms underlying the development of secondary malignancies following exposure to radiation; this is particularly important when estimating risk associated with highly heterogeneous dose distributions as is the case in the contralateral breast of women receiving breast cancer irradiation.

Teleradiology with satellite units - six years experience at the norwegian radium hospital.

UNLABELLED: Norway has played a leading role in Europe in applying telemedicine in health care services over the past two decades and is still in the forefront of developing telemedicine services both nationally and internationally. Today support for telemedicine comes mainly from the wish to meet the challenges of rising costs in health care. Critical obstacles for implementation of telemedicine techniques may by overcome easier by referring to the experience from other medical centers. A case in point is the six year experience of telemedicine at The Norwegian Radium Hospital, in distributing radiotherapy services to two satellite hospitals hundred kilometers far off. The main lesson learned is: the most serious obstacles are not technological but socio-psychological challenges and that staff up-dating, prior to implementation, is crucial. Case selections, routines, work flows and administrative solutions are described for the daily operations between the main clinic and the satellite units. IN CONCLUSION: radiotherapy service by telemedicine is feasible and cost effective. Standardization and quality assurance of radiotherapy at the quality level of a comprehensive cancer center can be offered to a much larger population and may play a role in improved cancer survival outcome.

Radiotherapy adapted to spatial and temporal variability in tumor hypoxia.

PURPOSE: To explore the feasibility and clinical potential of adapting radiotherapy to temporal and spatial variations in tumor oxygenation. METHODS AND MATERIALS: Repeated dynamic contrast enhanced magnetic resonance (DCEMR) images were taken of a canine sarcoma during the course of fractionated radiation therapy. The tumor contrast enhancement was assumed to represent the oxygen distribution. The IMRT plans were retrospectively adapted to the DCEMR images by employing tumor dose redistribution. Optimized nonuniform tumor dose distributions were calculated and compared with a uniform dose distribution delivering the same integral dose to the tumor. Clinical outcome was estimated from tumor control probability (TCP) and normal tissue complication probability (NTCP) modeling. RESULTS: The biologically adapted treatment was found to give a substantial increase in TCP compared with conventional radiotherapy, even when only pretreatment images were used as basis for the treatment planning. The TCP was further increased by repeated replanning during the course of treatment, and replanning twice a week was found to give near optimal TCP. Random errors in patient positioning were found to give a small decrease in TCP, whereas systematic errors were found to reduce TCP substantially. NTCP for the adapted treatment was similar to or lower than for the conventional treatment, both for parallel and serial normal tissue structures. CONCLUSION: Biologically adapted radiotherapy is estimated to improve treatment outcome of tumors having spatial and temporal variations in radiosensitivity.

Noninvasive monitoring of radiation-induced treatment response using proton magnetic resonance spectroscopy and diffusion-weighted magnetic resonance imaging in a colorectal tumor model.

BACKGROUND AND PURPOSE: To examine whether in vivo proton magnetic resonance spectroscopy ((1)H MRS) and diffusion-weighted magnetic resonance imaging (DW-MRI) can monitor radiation-induced changes in HT29 xenografts in mice. MATERIALS AND METHODS: HT29 xenografts in mice received a dose of 15Gy. In vivo(1)H MRS and DW-MRI were acquired pretreatment and 1, 3, 6 and 10 days post-irradiation. After imaging, tumors were excised for histological analysis. The amounts of necrosis, fibrosis and viable cells in the cross sections were scored and compared to changes in apparent diffusion coefficient (ADC) and choline/water ratio. RESULTS: Radiation-induced necrosis in the xenografts was observed as increased tumor ADC. In-growth of fibrosis three days post-irradiation restricting water mobility was accompanied by decreased tumor ADC. Choline/water ratio correlated with metabolic activity and tumor growth. CONCLUSIONS: ADC and choline/water ratio assessed by in vivo DW-MRI and (1)H MRS depicts radiation-induced changes in HT29 xenografts following irradiation.

Contralateral breast doses following radiotherapy of the breast and regional lymph nodes: Measurements and treatment planning calculations.

PURPOSE: To measure the dose distribution in the contralateral breast (CB) following radiotherapy of the breast and regional lymph nodes by a 4-field technique, and to examine whether related treatment planning calculations of CB doses reproduce the measurements. MATERIALS AND METHODS: CB doses were measured by thermoluminescence dosimetry on the surface of 8 patients and in an anthropomorphic phantom. Dose calculations at corresponding points of interest were performed by the treatment planning system Helax-TMS 6.1 using the pencil beam or the collapsed cone algorithm. RESULTS: The measured CB doses were typically between 1% and 15% of the prescribed dose. The dose decreased significantly both in the medial-lateral and cranial-caudal direction. The average ratio of the measured to the calculated CB dose was about 0.7 and 0.9 for the pencil beam and the collapsed cone algorithm, respectively. One of the treatment fields aimed at the regional lymph nodes and some of the chest wall gave the highest contribution to the CB dose. CONCLUSIONS: The dose distribution in the CB following locoregional radiotherapy of the breast and regional lymph nodes is quite inhomogeneous. The collapsed cone algorithm may be used for estimating doses to the CB. Some concern is raised regarding the current field arrangement and the consequences for the CB dose.

Proton therapy - a systematic review of clinical effectiveness.

BACKGROUND AND PURPOSE: Proton therapy is an emerging treatment modality for cancer that may have distinct advantages over conventional radiotherapy. This relates to its ability to confine the high-dose treatment area to the tumour volume and thus minimizing radiation dose to surrounding normal tissue. Several proton facilities are currently operating or under planning world-wide - in the United States, Asia and Europe. Until now no systematic review assessing the clinical effectiveness of this treatment modality has been published. MATERIALS AND METHODS: A systematic review of published studies that investigated clinical efficacy of proton therapy of cancer. RESULTS: We included 54 publications: 4 randomized controlled trials (RCTs) reported in 5 publications, 5 comparative studies and 44 case series. Two RCTs addressed proton irradiation as a boost following conventional radiation therapy for prostate cancer, where one demonstrated improved biochemical local control for the highest dose group without increased serious complication rates. Proton therapy has been used to treat a large number of patients with ocular tumours, but except for one low quality RCT, no proper comparison with other treatment alternatives has been undertaken. Proton therapy offers the option to deliver higher radiation doses and/or better confinement of the treatment of intracranial tumours in children and adults, but reported studies are heterogeneous in design and do not allow for strict conclusions. CONCLUSION: The evidence on clinical efficacy of proton therapy relies to a large extent on non-controlled studies, and thus is associated with low level of evidence according to standard heath technology assessment and evidence based medicine criteria.

Reconstruction of a ring applicator using CT imaging: impact of the reconstruction method and applicator orientation.

The purpose of this study is to investigate whether the method of applicator reconstruction and/or the applicator orientation influence the dose calculation to points around the applicator for brachytherapy of cervical cancer with CT-based treatment planning. A phantom, containing a fixed ring applicator set and six lead pellets representing dose points, was used. The phantom was CT scanned with the ring applicator at four different angles related to the image plane. In each scan the applicator was reconstructed by three methods: (1) direct reconstruction in each image (DR), (2) reconstruction in multiplanar reconstructed images (MPR) and (3) library plans, using pre-defined applicator geometry (LIB). The doses to the lead pellets were calculated. The relative standard deviation (SD) for all reconstruction methods was less than 3.7% in the dose points. The relative SD for the LIB method was significantly lower (p < 0.05) than for the DR and MPR methods for all but two points. All applicator orientations had similar dose calculation reproducibility. Using library plans for applicator reconstruction gives the most reproducible dose calculation. However, with restrictive guidelines for applicator reconstruction the uncertainties for all methods are low compared to other factors influencing the accuracy of brachytherapy.

Optimization of tumour control probability in hypoxic tumours by radiation dose redistribution: a modelling study.

Tumour hypoxia is a known cause of clinical resistance to radiation therapy. The purpose of this work was to model the effects on tumour control probability (TCP) of selectively boosting the dose to hypoxic regions in a tumour, while keeping the mean tumour dose constant. A tumour model with a continuous oxygen distribution, incorporating pO(2) histograms published for head and neck patients, was developed. Temporal and spatial variations in the oxygen distribution, non-uniform cell density and cell proliferation during treatment were included in the tumour modelling. Non-uniform dose prescriptions were made based on a segmentation of the tumours into four compartments. The main findings were: (1) Dose redistribution considerably improved TCP for all tumours. (2) The effect on TCP depended on the degree of reoxygenation during treatment, with a maximum relative increase in TCP for tumours with poor or no reoxygenation. (3) Acute hypoxia reduced TCP moderately, while underdosing chronic hypoxic cells gave large reductions in TCP. (4) Restricted dose redistribution still gave a substantial increase in TCP as compared to uniform dose boosts. In conclusion, redistributing dose according to tumour oxygenation status might increase TCP when the tumour response to radiotherapy is limited by chronic hypoxia. This could potentially improve treatment outcome in a subpopulation of patients who respond poorly to conventional radiotherapy.

On the parameter describing the generalised equivalent uniform dose (gEUD) for tumours.

The purpose of the present work was to estimate the parameter 'a' describing the generalised equivalent uniform dose (gEUD) for tumours and its dependence on radiobiological parameters. The consequences of uncertainties in a on the gEUD were also studied. An estimate of a was found by requiring that, for a given target dose distribution, the mechanistic EUD (based on radiobiological linear quadratic modelling) equals gEUD. The estimate of a was found to depend on the dose distribution, and decreased with factors that increase the slope of the cell survival curve (i.e. decreasing alpha/beta values and increasing alpha values). Furthermore, the parameter a was estimated for 35 prostate cancer IMRT plans of varying dose distributions, for two sets of previously published radiobiological parameters: (1) alpha=0.15 Gy(-1) and alpha/beta=3 Gy, and (2) alpha=0.26 Gy(-1) and alpha/beta=10 Gy. The estimated values of a ranged from -25.6 to -22.4 for all combinations of dose distributions and parameter sets. Uncertainties in a were found to give only small uncertainties in gEUD. Although the current work shows limitations of the gEUD model for tumours, gEUD may still be preferable for biological treatment plan optimization, evaluation and reporting.

Dose optimisation in single plane interstitial brachytherapy.

BACKGROUND AND PURPOSE: Brachytherapy dose distributions can be optimised by modulation of source dwell times. In this study dose optimisation in single planar interstitial implants was evaluated in order to quantify the potential benefit in patients. MATERIAL AND METHODS: In 14 patients, treated for recurrent rectal and cervical cancer, flexible catheters were sutured intra-operatively to the tumour bed in areas with compromised surgical margin. Both non-optimised, geometrically and graphically optimised CT -based dose plans were made. The overdose index (OI), homogeneity index (HI), conformal index (COIN), minimum target dose, and high dose volumes were evaluated. The dependence of OI, HI, and COIN on target volume and implant regularity was evaluated. In addition, 12 theoretical implant configurations were analyzed. RESULTS: Geometrical and graphical optimisation improved the dose plans significantly with graphical optimisation being superior. Graphically optimised dose plans showed a significant decrease of 18%+/-9% in high dose volume (p<0.001). HI, COIN, and OI were significantly improved from 0.50+/-0.05 to 0.60+/-0.05, from 0.65+/-0.04 to 0.71+/-0.04, and from 0.19+/-0.03 to 0.15+/-0.03, respectively (p<0.001 for all). Moreover, minimum target dose increased significantly from 71%+/-5% to 80%+/-5% (p<0.001). The improvement in OI and HI obtained by optimisation depended on the regularity of the implant, such that the benefit of optimisation was larger for irregular implants. OI and HI correlated strongly with target volume limiting the usability of these parameters for comparison of dose plans between patients. CONCLUSIONS: Dwell time optimisation significantly improved the dose distribution regarding homogeneity, conformity, minimum target dose, and size of high dose volumes. Graphical optimisation is fast, reproducible and superior to geometric optimisation.