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State of the art combined radiochemotherapy and image-guided brachytherapy for locally advanced cervical cancer (LACC) has shown improved disease control and survival as well as a significant reduction of organ related morbidity. However, LACC cancer survivors are still experiencing a spectrum of symptoms. The aim of this study was to identify co-occurring symptoms in cervix cancer survivors by using patient-reported outcome and physician assessed morbidity. EMBRACE I is a multicenter prospective observational study with 1416 LACC patients (2008–2015). Information on physician-assessed morbidity and patient-reported outcome was assessed at baseline and at regular follow-ups up with the CTCAE v.3 and EORTC-C30/CX24, respectively. Patients with at least 2 years of follow-up were included and data from 3 months to 2 years was used in the analysis. Factor analysis was used on both EORTC and CTCAE data with symptoms and follow-ups as observations. The extracted factors represent clusters of symptoms. Subsequently, regression models were built to investigate associations between the symptom clusters and QOL. The analysis included 742 patients. Despite the differences in the definition of physician-assessed and patient-reported symptoms, similar clusters are identified by the two assessment methods. Three main organ-related clusters are recognized for urinary, gastro-intestinal and vaginal morbidity. Furthermore, a general symptoms cluster where fatigue, pain, insomnia, neuropathy, and hot flashes have large weights is found. Lastly, a cluster with nausea, vomit and lack of appetite is also identified. The general, gastrointestinal and nausea clusters show significant associations with general QOL. This analysis on both PRO and physician-assessed morbidity found a cluster associated with general symptoms and organ-related symptom clusters (urinary, gastrointestinal, vaginal). This shows that LACC survivors experience a variety of co-occurring symptoms. Our analysis also shows that the cluster of general symptoms is associated with a decrease in QOL. [ABSTRACT FROM AUTHOR]

Strategies for minimizing irradiation of organs at risk (OARs) from pathological inguinal lymph node (PILN) boosting are needed to minimize the risk of morbidity. Coverage probability (CovP) is a conformal planning strategy for simultaneously integrated boost (SIB). Our aim was to investigate if SIB of PILN using CovP can be delivered safely in vulvar cancer. Ten consecutive patients treated with definitive radiotherapy (RT) including SIB of PILN and with daily cone beam CT (CBCT) were included. Dose prescription was 51.2/32 fx to the elective target and 64 Gy/32 fx to the gross disease at the vulva and to positive lymph nodes (LN). PILN were contoured on both planning CT and MRI (GTV-N) and combined to form ITV-N. Each PILN GTV-N was contoured on every third CBCT, in total 11 CBCT for each patient. OARs were subcutaneous tissue (SC), inguinal vessels, skin rim, bowel, and body contour. Three plans were created for every patient: A) Standard CT-based planning; PTV-N based on GTV-NCT with a 10 mm isotropic margin. B) CT and MRI-based planning with smaller margins: PTV-N based on ITV-N with a 5 mm isotropic margin. C) CovP. The total delivered dose to GTV-Ns was estimated by accumulating dose across all fractions based on GTV-Ns contoured on CBCT. Thirty-five PILNs were boosted. There was no significant difference in accumulated GTV-N D98% between the three plans. CovP delivered a higher mean dose to the GTV-N D50% and D2% (p < 0.001). The planned mean doses to the OARs were reduced when applying CovP. SIB of PILN in vulvar cancer based on CovP and a 5 mm PTV margin does not compromise target coverage during RT and reduces the dose to normal tissues in the groin. [ABSTRACT FROM AUTHOR]

Introduction:Density changes occurring during fractionated radiotherapy in the pelvic region may degrade proton dose distributions. The aim of the study was to quantify the dosimetric impact of gas cavities and body outline variations. Material and methods:Seven patients with locally advanced cervical cancer (LACC) were analyzed through a total of 175 daily cone beam computed tomography (CBCT) scans. Four-beams intensity-modulated proton therapy (IMPT) dose plans were generated targeting the internal target volume (ITV) composed of: primary tumor, elective and pathological nodes. The planned dose was 45 Gy [Relative-Biological-Effectiveness-weighted (RBE)] in 25 fractions and simultaneously integrated boosts of pathologic lymph nodes were 55–57.5 Gy (RBE). In total, 475 modified CTs were generated to evaluate the effect of: 1/gas cavities, 2/outline variations and 3/the two combined. The anatomy of each fraction was simulated by propagating gas cavities contours and body outlines from each daily CBCT to the pCT. Hounsfield units corresponding to gas and fat were assigned to the propagated contours. D98 (least dose received by the hottest 98% of the volume) and D99.9 for targets and V43Gy(RBE) (volume receiving ≥43 Gy(RBE)) for organs at risk (OARs) were recalculated on each modified CT, and total dose was evaluated through dose volume histogram (DVH) addition across all fractions. Results:Weight changes during radiotherapy were between −3.1% and 1.2%. Gas cavities and outline variations induced a median [range] dose degradation for ITV45 of 1.0% [0.5–3.5%] for D98 and 2.1% [0.8–6.4%] for D99.9. Outline variations had larger dosimetric impact than gas cavities. Worst nodal dose degradation was 2.0% for D98 and 2.3% for D99.9. The impact on bladder, bowel and rectum was limited with V43Gy(RBE) variations ≤3.5 cm3. Conclusion:Bowel gas cavities and outline variations had minor impact on accumulated dose in targets and OAR of four-field IMPT in a LACC population of moderate weight changes. [ABSTRACT FROM AUTHOR]

The article offers information on the 15th Acta Oncologica Symposium, held in Aarhus, Denmark on June 13–16, 2017 which was dedicated to Biology-Guided Adaptive Radiotherapy (BiGART). Topics discussed include the aim to the BiGART of treatment adaptation, the annual meeting of the European Network for LIGht ion Hadron Therapy, and the discussion on particle therapy at the meeting.

Introduction:More than 50% of patients with locally advanced cervical cancer (LACC) have pathological nodes. Coverage probability (CovP) is a new planning technique allowing for relaxed dose at the boost periphery minimising collateral irradiation. The aim was to report the first early clinical outcome data for CovP based simultaneous integrated boost (SIB) in LACC. Material and methods:Twenty-three consecutive node positive patients were analysed. FIGO stage IB2/IIB/IIIB/IVA/IVB was 1/14/3/1/4. Treatment was radio(chemo)therapy (RT) delivering 45 Gy/25 fx whole pelvis ± para-aortic region (PAN) using volumetric arc therapy (VMAT) followed by magnetic resonance imaging (MRI) guided brachytherapy. PAN RT (13 pts) was given if >2 nodes or if node(s) were present at the common iliac vessels or PAN. Nodal gross tumour volumes (GTV-N) were contoured on both PET-CT and MRI. Clinical target volume (CTV-N) was formed by fusion of GTV-NCTand GTV-NMRI. A 5-mm isotropic margin was used for planning target volume (PTV-N). Nodes in the small pelvis were boosted to 55.0 Gy/25 fx. Common iliac and para-aortic nodes received 57.5 Gy/25 fx. Planning aims for CovP were PTV-N D98 ≥ 90%, CTV-N D98 ≥ 100% and CTV-N D50 ≥ 101.5%. Results:Seventy-four nodes were boosted. A consistent 5.0 ± 0.7 Gy dose reduction from CTV-N D98to PTV-N D98was obtained. In total, 73/74 nodes were in complete remission at 3 months PET-CT and MRI. Pelvic control was obtained in 21/23 patients. One patient (IB2, clear cell) had salvageable local disease, while another (IIB) failed in a boosted node. Two patients failed in un-irradiated PAN. One patient age 88 (IIIB) did not receive PAN RT, despite a common iliac node. The other (IIB) recurred above L1. Two further patients (IVB) failed systemically. Conclusion:Since complete remission at 3 months is predictive for favourable long-term nodal control, our study indicates that CovP for SIB is promising. [ABSTRACT FROM AUTHOR]

Objective:To evaluate the role of interstitial pulsed dose rate brachytherapy (PDR-BT) in multimodality treatment of locally advanced primary or recurrent rectal and sigmoid cancer with high risk of microscopic incomplete resection (R1). Methods and material:A total of 73 consecutive patients (recurrent/primary: 40/33) were treated with PDR-BT between 2001 and 2010. Patients received preoperative external beam radiotherapy (EBRT) and concomitant chemotherapy. Following resection of the tumor and the involved pelvic organs, a median of four (3–8) catheters were sutured to the tumor bed with a distance of approximately 1 cm between the catheters. A target respecting the catheters with a margin of 5 mm was contoured on computed tomography (CT) and three-dimensional (3D) dose planning with a planning aim for BT of D90 > 30 Gy, (0.6 Gy/pulse, 1 pulse/h) was performed. Previously irradiated patients (27%) underwent surgery that was directly followed by PDR-BT. Postoperative EBRT was then applied to the tumor bed 3–5 weeks after PDR-BT. Results:A total of 23 patients (31%) received a radical resection (R0) and 45 patients (62%) received an R1 resection. Five patients (7%) received a macroscopic incomplete resection (R2). The five-year overall survival was 33%. Local control at five years was 67% for patients who received a R0 resection and 32% for patients who received an R1 resection. The five-year actuarial risk of a grade 3–4 BT-related complication was 5%. Conclusions:Meaningful disease control and survival can be obtained at an acceptable rate of late morbidity in selected patients with locally advanced primary and recurrent rectal or sigmoid cancer using (chemo) RT, extensive surgery and PDR-BT when a high risk of an R1 resection is expected. [ABSTRACT FROM PUBLISHER]

Introdution: Variation in shape, position and treatment response of both tumor and organs at risk are major challenges for accurate dose delivery in radiotherapy. Adaptive radiotherapy (ART) has been proposed to customize the treatment to these motion/response patterns of the individual patients, but increases workload and thereby challenges clinical implementation. This paper reviews strategies and workflows for clinical and in silico implemented ART for prostate, bladder, gynecological (gyne) and ano-rectal cancers.Material and methods: Initial identification of papers was based on searches in PubMed. For each tumor site, the identified papers were screened independently by two researches for selection of studies describing all processes of an ART workflow: treatment monitoring and evaluation, decision and execution of adaptations. Both brachytherapy and external beam studies were eligible for review.Results: The review consisted of 43 clinical studies and 51 in silico studies. For prostate, 1219 patients were treated with offline re-planning, mainly to adapt prostate motion relative to bony anatomy. For gyne 1155 patients were treated with online brachytherapy re-planning while 25 ano-rectal cancer patients were treated with offline re-planning, all to account for tumor regression detected by magnetic resonance imaging (MRI)/computed tomography (CT). For bladder and gyne, 161 and 64 patients, respectively, were treated with library-based online plan selection to account for target volume and shape variations. The studies reported sparing of rectum (prostate and bladder cancer), bladder (ano-rectal cancer) and bowel cavity (gyne and bladder cancer) as compared to non-ART.Conclusion: Implementations of ART were dominated by offline re-planning and online brachytherapy re-planning strategies, although recently online plan selection workflows have increased with the availability of cone-beam CT. Advantageous dosimetric and outcome patterns using ART was documented by the studies of this review. Despite this, clinical implementations were scarce due to challenges in target/organ re-contouring and suboptimal patient selection in the ART workflows. [ABSTRACT FROM AUTHOR]

Background. Diffusion-weighted magnetic resonance imaging (DW-MRI) and the derived apparent diffusion coefficient (ADC) value has potential for monitoring tumor response to radiotherapy (RT). Method used for segmentation of volumes with reduced diffusion will influence both volume size and observed distribution of ADC values. This study evaluates: 1) different segmentation methods; and 2) how they affect assessment of tumor ADC value during RT. Material and methods. Eleven patients with locally advanced cervical cancer underwent MRI three times during their RT: prior to start of RT (PRERT), two weeks into external beam RT (WK2RT) and one week prior to brachytherapy (PREBT). Volumes on DW-MRI were segmented using three semi-automatic segmentation methods: “cluster analysis”, “relative signal intensity (SD4)” and “region growing”. Segmented volumes were compared to the gross tumor volume (GTV) identified on T2-weighted MR images using the Jaccard similarity index (JSI). ADC values from segmented volumes were compared and changes of ADC values during therapy were evaluated. Results. Significant difference between the four volumes (GTV, DWIcluster, DWISD4and DWIregion) was found (p < 0.01), and the volumes changed significantly during treatment (p < 0.01). There was a significant difference in JSI among segmentation methods at time of PRERT (p < 0.016) with region growing having the lowest JSIGTV(mean± sd: 0.35 ± 0.1), followed by the SD4 method (mean± sd: 0.50 ± 0.1) and clustering (mean± sd: 0.52 ± 0.3). There was no significant difference in mean ADC value compared at same treatment time. Mean tumor ADC value increased significantly (p < 0.01) for all methods across treatment time. Conclusion. Among the three semi-automatic segmentations of hyper-intense intensities on DW-MR images implemented, cluster analysis and relative signal thresholding had the greatest similarity to the clinical tumor volume. Evaluation of mean ADC value did not depend on segmentation method. [ABSTRACT FROM PUBLISHER]

An introduction is presented in which the editor discusses publications that were presented at the 13th Acta Oncologica Symposium 2015 including functional imaging of tumors, biology-guided adaptive radiotherapy (BiGART), and clinical outcome of adaptive radiotherapy.

Background.Despite local control now exceeding 90% with image-guided adaptive brachytherapy (IGABT), regional and distant metastases continue to curb survival in locally advanced cervical cancer. As regional lymph nodes often represent first site of metastatic spread, improved nodal control could improve survival. The aim of this study was to examine optimal volume and dose of external beam radiotherapy (EBRT) to maximize regional control including dose contribution from IGABT. Material and methods.In total 139 patients from the EMBRACE study were analyzed. Individual nodal dose was determined by dose-maps from EBRT and IGABT. All PET/CT scans were re-evaluated and nodal maximal standard uptake value (SUVmax) was determined. Nodal failures were registered to planning scans and related to boosted nodes and treated volume. Relation between SUVmaxand nodal control as well as the pattern of regional nodal failure were analyzed. Results.Eighty-four patients were node positive. Nine patients had all metastatic nodes surgically removed. Seventy-five patients had 209 nodes boosted with EBRT. Median nodal boost dose was 62 Gy EQD2 (53–69 Gy EQD2). Median SUVmaxwas 6 (2–22). No patients had persistent nodal disease, but six patients recurred in a boosted node. SUVmaxwas significantly higher in nodes that recurred (p = 0.02). However, there was no correlation to nodal dose or volume. Twenty-one patients had a nodal failure including para-aortic nodal (PAN) metastases above the irradiated volume. Nine patients had a PAN-only failure. Patients receiving ≤ 4 cycles of weekly cisplatin had higher risk of nodal failure (p < 0.01). Conclusion.Current RT practice provides a high level of control in both boosted nodes and the elective irradiated regional target. However, a high nodal SUVmaxis a negative prognostic predictor for nodal control. Attention should be raised to administration of a complete schedule of concurrent chemotherapy as well as treatment of para-aortic nodes. [ABSTRACT FROM PUBLISHER]

Background. Methods to accurately accumulate doses in radiotherapy (RT) are important for tumour and normal tissues being influenced by geometric uncertainties. The purpose of this study was to investigate a pre-release deformable image registration (DIR)-based dose accumulation application, in the setting of prostate RT. Material and methods. Initially accumulated bladder and prostate doses were assessed (based on 8-9 repeat CT scans/patient) for nine prostate cancer patients using an intensity-based DIR and dose accumulation algorithm as provided by the Dynamic Adaptive Radiation Therapy (DART) software. The accumulated bladder and prostate dose-volume histograms (DVHs) were compared on a range of parameters (paired Wilcoxon signed-rank test, 5% significance level) to DVHs derived using an in-house developed dose accumulation method based on biomechanical, contour-driven DIR (SurfaceRegistration). Finally, both these accumulated dose distributions were compared to the 'static' DVH, assessed from the planning CT. Results. Over the population, doses accumulated with DART were overall lower than those from SurfaceRegistration (p < 0.05: D2%, gEUD and NTCP (bladder); Dmin (prostate)). The magnitude of these differences peaked for the bladder gEUD with a population median of 47 Gy for DART versus 57 Gy for SurfaceRegistration. Across the ten bladder dose/volume parameters investigated, the most pronounced individual differences were observed between the 'accumulated' DVHs and the 'static' DVHs, with deviations in mean dose up to 22 Gy. Conclusion. Substantial and significant differences were observed in the dose distributions between the two investigated DIR-based dose accumulation applications. The most pronounced individual differences were seen for the bladder and relative to the planned dose distribution, encouraging the use of repeat imaging data in RT planning and evaluation for this organ. [ABSTRACT FROM AUTHOR]

Background. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a unique capability to probe tumour microvasculature. Different analysis of the acquired data will possibly lead to different conclusions. Therefore, the objective of this study was to investigate under which conditions the Tofts (TM), extended Tofts (ETM), compartmental tissue uptake model (C-TU) and 2-compartment exchange model (2CXM) were the optimal tracer kinetic models (TKMs) for the analysis of DCE-MRI in patients with cervical cancer. Material and methods. Ten patients with locally advanced cervical cancer (FIGO: IIA/IIB/IIIB/IVA - 1/5/3/1) underwent DCE-MRI prior to radiotherapy. From the two-parameter TM it was possible to extract the forward volume transfer constant (Ktrans) and the extracellular-extravascular volume fraction (ve). From the three-parameter ETM, additionally the plasma volume fraction (vp) could be extracted. From the three-parameter C-TU it was possible to extract information about the blood flow (Fp), permeability-surface area product (PS) and vp. Finally, the four-parameter 2CXM extended the C-TU to include ve. For each voxel, corrected Akaike information criterion (AICc) values were calculated, taking into account both the goodness-of-fit and the number of model parameters. The optimal model was defined as the model with the lowest AICc. Results. All four TKMs were the optimal model in different contiguous regions of the cervical tumours. For the 24 999 analysed voxels, the TM was optimal in 17.0%, the ETM was optimal in 2.2%, the C-TU in 23.4% and the 2CXM was optimal in 57.3%. Throughout the tumour, a high correlation was found between Ktrans(TM) and Fp(2CXM), ρ = 0.91. Conclusion. The 2CXM was most often optimal in describing the contrast agent enhancement of pre-treatment cervical cancers, although this model broke down in a subset of the tumour voxels where overfitting resulted in non-physiological parameter estimates. Due to the possible overfitting of the 2CXM, the C-TU was found more robust and when 2CXM was excluded from comparison the C-TU was the preferred model. [ABSTRACT FROM AUTHOR]

Background. Geometrical distortion is a major obstacle for the use of echo planar diffusion-weighted magnetic resonance imaging (DW-MRI) in planning of radiotherapy. This study compares geometrical distortion correction methods of DW-MRI at time of brachytherapy (BT) in locally advanced cervical cancer patients. Material and methods. In total 21 examinations comprising DW-MRI, dual gradient echo (GRE) for B0 field map calculation and T2-weighted (T2W) fat-saturated MRI of eight patients with locally advanced cervical cancer were acquired during BT with a plastic tandem and ring applicator in situ. The ability of B0 field map correction (B0M) and deformable image registration (DIR) to correct DW-MRI geometric image distortion was compared to the non-corrected DW-MRI including evaluation of apparent diffusion coefficient (ADC) for the gross tumor volume (GTV). Results. Geometrical distortion correction decreased tandem displacement from 3.3 ± 0.9 mm (non-corrected) to 2.9 ± 1.0 mm (B0M) and 1.9 ± 0.6 mm (DIR), increased mean normalized cross-correlation from 0.69 ± 0.1 (non- corrected) to 0.70 ± 0.10 (B0M) and 0.77 ± 0.1 (DIR), and increased the Jaccard similarity coefficient from 0.72 ± 0.1 (non-corrected) to 0.73 ± 0.06 (B0M) and 0.77 ± 0.1 (DIR). For all parameters only DIR corrections were significant (p < 0.05). ADC of the GTV did not change significantly with either correction method. Conclusion. DIR significantly improved geometrical accuracy of DW-MRI, with remaining residual uncertainties of less than 2 mm, while no significant improvement was seen using B0 field map correction [ABSTRACT FROM AUTHOR]

Background. The first Nordic protocol for three-dimensional (3D) planned radiotherapy in locally advanced cervical cancer was the prospective NOCECA study (1994-2000). NOCECA consisted of computed tomography (CT)-based 3D conformal external beam radiotherapy (EBRT) with a simultaneous integrated boost (SIB) to the primary tumour combined with brachytherapy (BT) based on x-ray imaging. In NOCECA the planning aim was to achieve 80 Gy at point A from EBRT and BT combined. However, the balance of dose between EBRT and BT was determined by tumour size at diagnosis with more EBRT dose given to point A and less by BT in more advanced stages. In 2005 image-guided adaptive brachytherapy (IGABT) based on magnetic resonance imaging (MRI) and optimisation of the BT dose distribution to the remaining tumour and cervix at time of BT (HR CTV) was introduced in Aarhus. EBRT remained like in NOCECA until 2008 when the SIB to the primary tumour was abandoned and IMRT was introduced as routine technique. In this study, we report outcome of our first five-year experience with IGABT using our NOCECA cohort as reference. Material and methods. The NOCECA cohort comprising 99 patients was compared with 140 consecutive patients treated by IGABT. Patients with para-aortic nodes were excluded in NOCECA but were present in 9% of the patients treated with IGABT. No patient in NOCECA received chemotherapy whereas concomitant cisplatin was given to 79% of the IGABT patients. Results. With IGABT actuarial local control was 91% at three years. When comparing NOCECA with IGABT overall survival was significantly improved from 63% to 79% (p = 0.005). In parallel, both moderate and severe late morbidity were reduced by about 50% (p = 0.02). Conclusion. Introduction of IGABT reduced morbidity and generated a very high rate of local control, which likely has improved survival by at least as much as concomitant chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose. Dynamic contrast enhanced (DCE) imaging has gained interest as an imaging modality for assessment of tumor characteristics and response to cancer treatment. However, for DCE-magnetic resonance imaging (MRI) tissue contrast enhancement may vary depending on imaging sequence and temporal resolution. The aim of this study is to compare DCE-MRI to DCE-computed tomography (DCE-CT) as the gold standard. Material and methods. Thirteen patients with advanced cervical cancer were scanned once prior to chemo-radiation and during chemo-radiation with DCE-CT and -MRI in immediate succession. A total of 22 paired DCE-CT and -MRI scans were acquired for comparison. Kinetic modeling using the extended Tofts model was applied to both image series. Furthermore the similarity of the spatial distribution was evaluated using a Γ analysis. The correlation between the two imaging techniques was evaluated using Pearson's correlation and the parameter means were compared using a Student's t-test (p < 0.05). Results. A significant positive correlation between DCE-CT and -MRI was found for all kinetic parameters. The results showing the best correlation with the DCE-CT-derived parameters were obtained using a population-based input function for MRI. The median Pearson's correlations were: volume transfer constant Ktrans (r = 0.9), flux rate constant kep (r = 0.77), extracellular volume fraction ve (r = 0.58) and blood plasma volume fraction vp (r = 0.83). All quantitative parameters were found to be significantly different as estimated by DCE-CT and -MRI. The Γ analysis in normalized maps revealed that 45% of the voxels failed to find a voxel with the corresponding value allowing for an uncertainty of 3 mm in position and 3% in value (Γ3,3). By reducing the criteria, the Γ-failure rates were: Γ3,5 (37% failure), Γ3,10 (26% failure) and at Γ3,15 (19% failure). Conclusion. Good to excellent correlations but significant bias was found between DCE-CT and -MRI. Both the Pearson's correlation and the Γ analysis proved that the spatial information was similar when analyzing the two sets of DCE data using the extended Tofts model. Improvement of input function sampling is needed to improve kinetic quantification using DCE-MRI. [ABSTRACT FROM AUTHOR]

Background. Diffusion weighted imaging (DWI) has gained interest as an imaging modality for assessment of tumor extension and response to cancer treatment. The purpose of this study is to assess the impact of the choice of b-values on the calculation of the Apparent Diffusion Coefficient (ADC) for locally advanced gynecological cancer and to estimate a stable interval of diffusion gradients that allows for best comparison of the ADC between patients and institutions. Material and methods. Six patients underwent a high resolution single shot EPI based DWI scan with 16 different diffusion gradients on a 3 Tesla Philips Achieva MR-scanner. Data analysis was performed by applying a monoexponential and a biexponential model to the acquired data. The biexponential function models the effect of both perfusion and diffusion. Results and conclusion. ADC changes of up to 40% were seen with the use of different b-values. Using a lower b-value ≥ 150 s/mm2 and an upper b-value ≥ 700 s/mm2 limited the variation to less that 10% from the reference ADC value. By eliminating the contribution of perfusion the uncertainty of quantitative ADC values were significantly reduced. [ABSTRACT FROM AUTHOR]

Background and purpose. T2 weighted MRI is recommended for image guided adaptive brachytherapy (IGABT) in cervical cancer. Diffusion weighted imaging (DWI) and the derived apparent diffusion coefficient (ADC) may add additional biological information on tumour cell density. The purpose of this study was to evaluate the distribution of the ADC within target volumes as recommended by GEC-ESTRO: Gross Tumour Volume at BT (GTVBT), High-Risk Clinical Tumour Volume (HR-CTV) and Intermediate-Risk Clinical Target Volume (IR-CTV) and to evaluate the change of diffusion between fractions of IGABT. Material and methods. Fifteen patients with locally advanced cervical cancer were examined by MRI before their first (BT1) and second (BT2) fraction of IGABT, resulting in a total of 30 MR examinations including both T2 weighted and DWI sequences. The Apparent Diffusion Coefficient (ADC) was calculated by use of three levels of b-values (0, 600, 1000 s/mm2). ADC maps were constructed and fused with the GEC ESTRO target contours. The mean ADC value within each target volume was calculated. Furthermore, volumes of low diffusion (ADClow) were defined based on an ADC threshold of 1.2 × 10−3 mm2/s, and overlap with target volumes was evaluated. Change of ADC level in target volumes and change of ADClow volume from BT1 to BT2 was also evaluated. Results. The mean ADC was significantly lower in GTVBT than in HR-CTV (p<0.001) which again was significantly lower than in IR-CTV (p<0.001). There was no significant change of the ADClow volume or ADC level within each target structure between BT1 and BT2 (p=0.242). All three GEC-ESTRO volumes contained volumes with low diffusion. The GTVBT contained 37.2% volume of low diffusion, HR-CTV 20.3% and IR-CTV 10.8%. Conclusion. With DWI we were able to find a significant difference in ADC-values for the three different GEC ESTRO targets. This supports the assumption that the target volumes used for dose prescription in IGABT contain tissues with different characteristics, with the tumour (GTVBT) being the volume with the lowest diffusion. No significant changes were found from BT1 to BT2 indicating that changes of ADC level and volumes are stable at the time of BT. Further studies are needed to evaluate the role of DWI in target contouring and dose prescription for IGABT. [ABSTRACT FROM AUTHOR]

Materials and methods. Two registration methods based on optical flow estimation have been programmed to run on a graphics programming unit (GPU). One of these methods by Horn & Schunck is tested on a 4DCT thorax data set with 10 phases and 41 landmarks identified per phase. The other method by Cornelius & Kanade is tested on a series of six 3D cone beam CT (CBCT) data sets and a conventional planning CT data set from a head and neck cancer patient. In each of these data sets 6 landmark points have been identified on the cervical vertebrae and the base of skull. Both CBCT to CBCT and CBCT to CT registration is performed. Results. For the 4DCT registration average landmark error was reduced by deformable registration from 3.5±2.0mm to 1.1±0.6mm. For CBCT to CBCT registration the average bone landmark error was 1.8±1.0mm after rigid registration and 1.6±0.8mm after deformable registration. For CBCT to CT registration errors were 2.2±0.6mm and 1.8±0.6mm for rigid and deformable registration respectively. Using GPU hardware the Horn & Schunck method was accelerated by a factor of 48. The 4DCT registration can be performed in 37seconds. The head and neck cancer patient registration takes 64seconds. Discussion. Compared to image slice thickness, which limits accuracy of landmark point determination, we consider the landmark point accuracy of the registration acceptable. The points identified in the CBCT images do not give a full impression of the result of doing deformable registration as opposed to rigid registration. A larger validation study is being planned in which soft tissue landmarks will facilitate tracking the deformable registration. The acceleration obtained using GPU hardware means that registration can be done online for CBCT. [ABSTRACT FROM AUTHOR]

Introduction. Image guided adaptive brachytherapy (IGABT) for cervical cancer, using mainly MRI, is an evolving method, increasingly replacing the 2D approach based on conventional radiography. During the complex 4D chain of this procedure image-assistance is provided for disease assessment, provisional treatment planning (“pre-planning”), applicator placement and reconstruction, as well as for contouring, definitive treatment planning and quality control of dose delivery. With IGABT changes of topography adjacent to the applicator, caused by tumour regression, oedema, organ changes and dilation are identified. Thus, the CTV for IGABT is primarily based on the tumour volume at the time of BT and takes into account both time and spatial domains. IGABT requires systematic concepts for target, OAR, biological modelling, DVH analysis, and dose-volume-adaptation. Methods and Results. This report focuses on the advantages and uncertainties, dose-effect relations and clinical results of the IGABT procedure addressing the current status and future perspectives. Uncertainties during the 4D chain of IGABT are mainly related to target contouring, applicator reconstruction, as well as to inter-fraction, intra-fraction and inter-application variability, as caused by tumour response and organ changes. Different from EBRT where set-up uncertainties are compensated by adding a margin to the CTV, no margins to the lateral and anterior-posterior directions can be used for IGABT. Discussion. By 3D treatment planning for IGABT significant improvement of the DVH parameters is achieved compared to 2D library plans. In small tumours the benefit is primarily obtained by a decrease of dose to nearby OAR while in large tumours the use of supplementary interstitial techniques and optimization may double the target volume that can be treated at a therapeutic dose level. The clinical impact of IGABT could recently be demonstrated by the establishment of some correlations between target- and organ-related DVH parameters versus disease control and side effects, which need further clarification. Overall, a very high local control rate can be achieved with minor treatment related morbidity. This favourable therapeutic ratio seems to be now reproducible under different conditions at various treatment centres. These results have to be validated within the upcoming multi-centre prospective IntErnational study on MRI-guided brachytherapy in locally advanced cervical cancer (EMBRACE). [ABSTRACT FROM AUTHOR]

Purpose. Locally advanced cervical cancer is usually treated with external beam radiotherapy followed by brachytherapy (BT). However, if response or tumour topography is unfavourable it may be difficult to reach a sufficient BT dose. The purpose of this study was to explore whether an applicator guided stereotactic IMRT boost could be combined with brachytherapy to improve dose volume parameters. Material and methods. Dose plans of 6 patients with HR CTV volumes of 31-100cc at the time of BT were analysed. MRI was performed with a combined intracavitary (IC)-interstitial (IS) ring applicator in situ. A radiotherapy schedule consisting of 45Gy (1.8Gy×25) IMRT followed by boost of 28Gy (7Gy×4fx) was modelled. Four different boost techniques were evaluated: IC-BT, IC/IS-BT, IC-BT+IMRT and IMRT. Dose plans were optimised for maximal tumour dose (D90) and coverage (V85Gy) while respecting DVH constraints in organs at risk: D2cc <75Gy in rectum and sigmoid and <90Gy in bladder (EQD2). In combined BT+IMRT dose plans, the IMRT plan was optimised on top of the BT dose distribution. Volumes irradiated to more than 60 Gy EQD2 (V60Gy) were evaluated. Results. Median dose coverage in IC plans was 74% [66-93%]. By using IC/IS or IC-BT+IMRT boost, the median coverage was improved to 95% [78-99%], and to 96% [69-99%] respectively. For IMRT alone, a median coverage of 98% [90-100%] was achieved, but V60Gy volumes were significantly increased by a median factor of 2.0 [1.4-2.3] as compared to IC/IS. It depended on the individual tumour topography whether IC/IS-BT or IC-BT+IMRT boost was the most favourable technique. Conclusion. It is technically possible to create dose plans that combine image guided BT and IMRT. In this study the dose coverage could be significantly increased by adding IS-BT or IMRT boost to the intracavitary dose. Using IMRT alone for boost cannot be advocated since this results in a significant increase of the volume irradiated to 60Gy. [ABSTRACT FROM AUTHOR]