Reducing the lateral dose penumbra in IMPT by incorporating transmission pencil beams.

OBJECTIVE: In intensity-modulated proton therapy (IMPT), Bragg peaks result in steep distal dose fall-offs, while the lateral IMPT dose fall-off is often less steep than in photon therapy. High-energy pristine transmission ('shoot through') pencil beams have no Bragg peak in the patient, but show a sharp lateral penumbra at the target level. We investigated whether combining Bragg peaks with Transmission pencil beams('IMPT&TPB') could improve head-and-neck plans by exploiting the steep lateral dose fall-off of transmission pencil beams. APPROACH: Our system for automated multi-criteria IMPT plan optimisation was extended for combined optimisation of BPs and TPBs. The system generates for each patient a Pareto-optimal plan using a generic 'wish-list' with prioritised planning objectives and hard constraints. For eight nasopharynx cancer patients (NPC) and eight oropharynx cancer (OPC) patients, the IMPT&TPB plan was compared to the competing conventional IMPT plan with only Bragg peaks, which was generated with the same optimiser, but without transmission pencil beams. MAIN RESULTS: Clinical OAR and target constraints were met in all plans. By allowing transmission pencil beams in the optimisation, on average 14 of the 25 investigated OAR plan parameters significantly improved for NPC, and 9 of the 17 for OPC, while only one OPC parameter showed small but significant deterioration. Non-significant differences were found in the remaining parameters. In NPC, cochlea Dmean reduced by up to 17.5 Gy and optic nerve D2% by up to 11.1 Gy. CONCLUSION: Compared to IMPT, IMPT&TPB resulted in comparable target coverage with overall superior OAR sparing, the latter originating from steeper dose fall-offs close to OARs.

SISS-MCO: large scale sparsity-induced spot selection for fast and fully-automated robust multi-criteria optimisation of proton plans.

Objective.Intensity modulated proton therapy (IMPT) is an emerging treatment modality for cancer. However, treatment planning for IMPT is labour-intensive and time-consuming. We have developed a novel approach for multi-criteria optimisation (MCO) of robust IMPT plans (SISS-MCO) that is fully automated and fast, and we compare it for head and neck, cervix, and prostate tumours to a previously published method for automated robust MCO (IPBR-MCO, van de Water 2013).Approach.In both auto-planning approaches, the applied automated MCO of spot weights was performed with wish-list driven prioritised optimisation (Breedveld 2012). In SISS-MCO, spot weight MCO was applied once for every patient after sparsity-induced spot selection (SISS) for pre-selection of the most relevant spots from a large input set of candidate spots. IPBR-MCO had several iterations of spot re-sampling, each followed by MCO of the weights of the current spots.Main results.Compared to the published IPBR-MCO, the novel SISS-MCO resulted in similar or slightly superior plan quality. Optimisation times were reduced by a factor of 6 i.e. from 287 to 47 min. Numbers of spots and energy layers in the final plans were similar.Significance.The novel SISS-MCO automatically generated high-quality robust IMPT plans. Compared to a published algorithm for automated robust IMPT planning, optimisation times were reduced on average by a factor of 6. Moreover, SISS-MCO is a large scale approach; this enables optimisation of more complex wish-lists, and novel research opportunities in proton therapy.

Surrogate-free machine learning-based organ dose reconstruction for pediatric abdominal radiotherapy.

To study radiotherapy-related adverse effects, detailed dose information (3D distribution) is needed for accurate dose-effect modeling. For childhood cancer survivors who underwent radiotherapy in the pre-CT era, only 2D radiographs were acquired, thus 3D dose distributions must be reconstructed from limited information. State-of-the-art methods achieve this by using 3D surrogate anatomies. These can however lack personalization and lead to coarse reconstructions. We present and validate a surrogate-free dose reconstruction method based on Machine Learning (ML). Abdominal planning CTs (n = 142) of recently-treated childhood cancer patients were gathered, their organs at risk were segmented, and 300 artificial Wilms' tumor plans were sampled automatically. Each artificial plan was automatically emulated on the 142 CTs, resulting in 42,600 3D dose distributions from which dose-volume metrics were derived. Anatomical features were extracted from digitally reconstructed radiographs simulated from the CTs to resemble historical radiographs. Further, patient and radiotherapy plan features typically available from historical treatment records were collected. An evolutionary ML algorithm was then used to link features to dose-volume metrics. Besides 5-fold cross validation, a further evaluation was done on an independent dataset of five CTs each associated with two clinical plans. Cross-validation resulted in mean absolute errors ≤ 0.6 Gy for organs completely inside or outside the field. For organs positioned at the edge of the field, mean absolute errors ≤ 1.7 Gy for [Formula: see text], ≤ 2.9 Gy for [Formula: see text], and ≤ 13% for [Formula: see text] and [Formula: see text], were obtained, without systematic bias. Similar results were found for the independent dataset. To conclude, we proposed a novel organ dose reconstruction method that uses ML models to predict dose-volume metric values given patient and plan features. Our approach is not only accurate, but also efficient, as the setup of a surrogate is no longer needed.

Analysis of 105.000 patients with cancer: have they been discussed in oncologic multidisciplinary team meetings? A nationwide population-based study in the Netherlands.

INTRODUCTION: For optimal oncological care, it is recommended to discuss every patient with cancer in a multidisciplinary team meeting (MDTM). This is a time consuming and expensive practice, leading to a growing demand to change the current workflow. We aimed to investigate the number of patients discussed in MDTMs and to identify characteristics associated with not being discussed. METHODS: Data of patients with a newly diagnosed solid malignant tumour in 2015 and 2016 were analysed through the nationwide population-based Netherlands Cancer Registry (NCR). We clustered tumour types in groups that were frequently discussed within a tumour-specific MDTM. Tumour types without information about MDTMs in the NCR were excluded. Multivariable logistic regression analyses were used to analyse factors associated with not being discussed. RESULTS: Out of 105.305 patients with cancer, 91% were discussed in a MDTM, varying from 74% to 99% between the different tumour groups. Significantly less frequently discussed were patients aged ≥75 years (odds ratio [OR] = 0.7, 95% confidence interval [CI] = 0.6-0.7), patients diagnosed with disease stage I (OR = 0.5, 95% CI = 0.5-0.6), IV (OR = 0.4, 95% CI = 0.4-0.4) or unknown (OR = 0.2, 95% CI = 0.2-0.2) and patients who received no treatment (OR = 0.3, 95% CI = 0.3-0.3). Patients who received a multidisciplinary treatment were more likely to be discussed in contrary to a monodisciplinary treatment (OR = 4.6, 95% CI = 4.2-5.1). CONCLUSION: In general, most patients with cancer were actually discussed in a MDTM, although differences were observed between tumour groups. Factors associated with not being discussed may, at least partially, reflect the absence of a multidisciplinary question. These results form a starting point for debate on a more durable and efficient new MDTM strategy.

Dosimetric comparison of library of plans and online MRI-guided radiotherapy of cervical cancer in the presence of intrafraction anatomical changes.

BACKGROUND: Online magnetic resonance imaging (MRI)-guided radiotherapy of cervical cancer has the potential to further reduce dose to organs at risk (OAR) as compared to a library of plans (LOP) approach. This study presents a dosimetric comparison of an MRI-guided strategy with a LOP strategy taking intrafraction anatomical changes into account. METHODS: The 14 patients included in this study were treated with chemo radiation at our institute and received weekly MRIs after informed consent. The MRI-guided strategy consisted of treatment plans created on the weekly sagittal MRI with 3 mm and 5 mm planning target volume (PTV) margin for clinical target volume (CTV) cervix-uterus (MRI_3mm and MRI_5mm). The plans for the LOP strategy were based on interpolations of CTV cervix-uterus on pretreatment full and empty bladder scans. Dose volume histogram (DVH) parameters were compared for targets and OARs as delineated on the weekly transversal MRI, which was acquired on average 10 min after the sagittal MRI. RESULTS: For the MRI_5mm strategy D98% of the high-risk CTV was at least 95% for all weekly MRIs of all patients, while for the LOP and MRI_3mm strategy this requirement was not satisfied for at least one weekly MRI for 1 and 3 patients, respectively. The average reduction of the volume of the reference dose (95% of the prescribed dose) as compared to the LOP strategy was 464 cm3 for the MRI_3mm strategy, and 422 cm3 for the MRI_5mm strategy. The bowel bag constraint V40Gy < 350 cm3 was violated for 13 patients for the LOP strategy and for 5 patients for both MRI_3mm and MRI_5mm strategy. CONCLUSIONS: With online MRI-guided radiotherapy of cervical cancer considerable sparing of OARs can be achieved. If a new treatment plan can be generated and delivered within 10 min, an online MRI-guided strategy with a 5 mm PTV margin for CTV cervix-uterus is sufficient to account for intrafraction anatomical changes. TRIAL REGISTRATION: NL44492.018.13.

Impact of setup and range uncertainties on TCP and NTCP following VMAT or IMPT of oropharyngeal cancer patients.

Setup and range uncertainties compromise radiotherapy plan robustness. We introduce a method to evaluate the clinical effect of these uncertainties on the population using tumor control probability (TCP) and normal tissue complication probability (NTCP) models. Eighteen oropharyngeal cancer patients treated with curative intent were retrospectively included. Both photon (VMAT) and proton (IMPT) plans were created using a planning target volume as planning objective. Plans were recalculated for uncertainty scenarios: two for range over/undershoot (IMPT) or CT-density scaling (VMAT), six for shifts. An average shift scenario ([Formula: see text]) was calculated to assess random errors. Dose differences between nominal and scenarios were translated to TCP (2 models) and NTCP (15 models). A weighted average (W_Avg) of the TCP\NTCP based on Gaussian distribution over the variance scenarios was calculated to assess the clinical effect of systematic errors on the population. TCP/NTCP uncertainties were larger in IMPT compared to VMAT. Although individual perturbations showed risks of plan deterioration, the [Formula: see text] scenario did not show a substantial decrease in any of the TCP endpoints suggesting evaluated plans in this cohort were robust for random errors. Evaluation of the W_Avg scenario to assess systematic errors showed in VMAT no substantial decrease in TCP endpoints and in IMPT a limited decrease. In IMPT, the W_Avg scenario had a mean TCP loss of 0%-2% depending on plan type and primary or nodal control. The W_Avg for NTCP endpoints was around 0%, except for mandible necrosis in IMPT (W_Avg: 3%). The estimated population impact of setup and range uncertainties on TCP/NTCP following VMAT or IMPT of oropharyngeal cancer patients was small for both treatment modalities. The use of TCP/NTCP models allows for clinical interpretation of the population effect and could be considered for incorporation in robust evaluation methods. Highlights: - TCP/NTCP models allow for a clinical evaluation of uncertainty scenarios. - For this cohort, in silico-PTV based IMPT plans and VMAT plans were robust for random setup errors. - Effect of systematic errors on the population was limited: mean TCP loss was 0%-2%.

Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer.

BACKGROUND: Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer. METHODS: MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment. RESULTS: In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8 months for neoadjuvant treatment and 14·8 months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0 months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P < 0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P < 0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P = 0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P < 0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients. CONCLUSION: Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374.

Beam configuration selection for robust intensity-modulated proton therapy in cervical cancer using Pareto front comparison.

The Pareto front reflects the optimal trade-offs between conflicting objectives and can be used to quantify the effect of different beam configurations on plan robustness and dose-volume histogram parameters. Therefore, our aim was to develop and implement a method to automatically approach the Pareto front in robust intensity-modulated proton therapy (IMPT) planning. Additionally, clinically relevant Pareto fronts based on different beam configurations will be derived and compared to enable beam configuration selection in cervical cancer proton therapy. A method to iteratively approach the Pareto front by automatically generating robustly optimized IMPT plans was developed. To verify plan quality, IMPT plans were evaluated on robustness by simulating range and position errors and recalculating the dose. For five retrospectively selected cervical cancer patients, this method was applied for IMPT plans with three different beam configurations using two, three and four beams. 3D Pareto fronts were optimized on target coverage (CTV D(99%)) and OAR doses (rectum V30Gy; bladder V40Gy). Per patient, proportions of non-approved IMPT plans were determined and differences between patient-specific Pareto fronts were quantified in terms of CTV D(99%), rectum V(30Gy) and bladder V(40Gy) to perform beam configuration selection. Per patient and beam configuration, Pareto fronts were successfully sampled based on 200 IMPT plans of which on average 29% were non-approved plans. In all patients, IMPT plans based on the 2-beam set-up were completely dominated by plans with the 3-beam and 4-beam configuration. Compared to the 3-beam set-up, the 4-beam set-up increased the median CTV D(99%) on average by 0.2 Gy and decreased the median rectum V(30Gy) and median bladder V(40Gy) on average by 3.6% and 1.3%, respectively. This study demonstrates a method to automatically derive Pareto fronts in robust IMPT planning. For all patients, the defined four-beam configuration was found optimal in terms of plan robustness, target coverage and OAR sparing.

Quantification of image distortions on the Utrecht interstitial CT/MR brachytherapy applicator at 3T MRI.

PURPOSE: To quantify distortions on MR images of the Utrecht interstitial CT/MR applicator at a field strength of 3T using an MRI-only method. MATERIALS AND METHODS: An MR-compatible phantom suspending the applicator in water was built and imaged on a Philips Ingenia 3T MRI scanner. A map of the magnetic field (B0) was calculated from multiecho images and used to quantify the field inhomogeneity. The expected displacements of the applicator could be quantified using the measured field inhomogeneity and sequence bandwidth. Additionally, two scans were acquired using opposing readout gradients. These scans were rigidly matched and their displacement was compared with the expected displacements from the B0 map. These same methods were applied in 4 patients. By rigid matching of the scans acquired with opposing readout direction the applicator displacement due to image distortion from B0 inhomogeneity as well as patient movement and organ deformation was determined. RESULTS: According to the B0 map, the displacement on the intrauterine device of the plastic brachytherapy applicator was <0.4 mm for both the phantom and patients. Displacements obtained by the opposing readout method were ≤0.8 mm for each patient with a mean ± SD over the patients of 0.3 ± 0.1 mm. CONCLUSION: The results of our study indicate that the B0 method agrees with the opposing readout method. Displacements caused by magnetic field inhomogeneity on 3T MRI were small compared with displacements due to patient movement and organ deformation.

Induction chemotherapy with docetaxel/cisplatin/5-fluorouracil followed by randomization to two cisplatin-based concomitant chemoradiotherapy schedules in patients with locally advanced head and neck cancer (CONDOR study) (Dutch Head and Neck Society 08-01): A randomized phase II study.

PURPOSE: To study the feasibility of induction chemotherapy added to concomitant cisplatin-based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer (LAHNC). PATIENTS AND METHODS: LAHNC patients were treated with 4 courses of docetaxel/cisplatin/5-fluorouracil (TPF) followed by randomization to either cisplatin 100 mg/m(2) with conventional radiotherapy (cis100 + RT) or cisplatin 40 mg/m(2) weekly with accelerated radiotherapy (cis40 + ART). Primary endpoint was feasibility, defined as receiving ≥ 90% of the scheduled total radiation dose. Based on power analysis 70 patients were needed. RESULTS: 65 patients were enrolled. The data safety monitoring board advised to prematurely terminate the study, because only 22% and 41% (32% in total) of the patients treated with cis100 + RT (n = 27) and cis40 + ART (n = 29) could receive the planned dose cisplatin during CRT, respectively, even though the primary endpoint was reached. Most common grade 3-4 toxicity was febrile neutropenia (18%) during TPF and dehydration (26% vs 14%), dysphagia (26% vs 24%) and mucositis (22% vs 57%) during cis100 + RT and cis40 + ART, respectively. For the patients treated with cis100 + RT and cis40 + ART, two years progression free survival and overall survival were 70% and 78% versus 72% and 79%, respectively. CONCLUSION: After TPF induction chemotherapy, cisplatin-containing CRT is not feasible in LAHNC patients, because the total planned cisplatin dose could only be administered in 32% of the patients due to toxicity. However, all but 2 patients received more than 90% of the planned radiotherapy. Clinical Trials Information: NCT00774319.

Automatic detection system for multiple region of interest registration to account for posture changes in head and neck radiotherapy.

Despite immobilization of head and neck (H and N) cancer patients, considerable posture changes occur over the course of radiotherapy (RT). To account for the posture changes, we previously implemented a multiple regions of interest (mROIs) registration system tailored to the H and N region for image-guided RT correction strategies. This paper is focused on the automatic segmentation of the ROIs in the H and N region. We developed a fast and robust automatic detection system suitable for an online image-guided application and quantified its performance. The system was developed to segment nine high contrast structures from the planning CT including cervical vertebrae, mandible, hyoid, manubrium of sternum, larynx and occipital bone. It generates nine 3D rectangular-shaped ROIs and informs the user in case of ambiguities. Two observers evaluated the robustness of the segmentation on 188 H and N cancer patients. Bland-Altman analysis was applied to a sub-group of 50 patients to compare the registration results using only the automatically generated ROIs and those manually set by two independent experts. Finally the time performance and workload were evaluated. Automatic detection of individual anatomical ROIs had a success rate of 97%/53% with/without user notifications respectively. Following the notifications, for 38% of the patients one or more structures were manually adjusted. The processing time was on average 5 s. The limits of agreement between the local registrations of manually and automatically set ROIs was comprised between ±1.4 mm, except for the manubrium of sternum (-1.71 mm and 1.67 mm), and were similar to the limits agreement between the two experts. The workload to place the nine ROIs was reduced from 141 s (±20 s) by the manual procedure to 59 s (±17 s) using the automatic method. An efficient detection system to segment multiple ROIs was developed for Cone-Beam CT image-guided applications in the H and N region and is clinically implemented in our department.

Generic method for automatic bladder segmentation on cone beam CT using a patient-specific bladder shape model.

PURPOSE: The aim of this study is to develop and validate a generic method for automatic bladder segmentation on cone beam computed tomography (CBCT), independent of gender and treatment position (prone or supine), using only pretreatment imaging data. METHODS: Data of 20 patients, treated for tumors in the pelvic region with the entire bladder visible on CT and CBCT, were divided into four equally sized groups based on gender and treatment position. The full and empty bladder contour, that can be acquired with pretreatment CT imaging, were used to generate a patient-specific bladder shape model. This model was used to guide the segmentation process on CBCT. To obtain the bladder segmentation, the reference bladder contour was deformed iteratively by maximizing the cross-correlation between directional grey value gradients over the reference and CBCT bladder edge. To overcome incorrect segmentations caused by CBCT image artifacts, automatic adaptations were implemented. Moreover, locally incorrect segmentations could be adapted manually. After each adapted segmentation, the bladder shape model was expanded and new shape patterns were calculated for following segmentations. All available CBCTs were used to validate the segmentation algorithm. The bladder segmentations were validated by comparison with the manual delineations and the segmentation performance was quantified using the Dice similarity coefficient (DSC), surface distance error (SDE) and SD of contour-to-contour distances. Also, bladder volumes obtained by manual delineations and segmentations were compared using a Bland-Altman error analysis. RESULTS: The mean DSC, mean SDE, and mean SD of contour-to-contour distances between segmentations and manual delineations were 0.87, 0.27 cm and 0.22 cm (female, prone), 0.85, 0.28 cm and 0.22 cm (female, supine), 0.89, 0.21 cm and 0.17 cm (male, supine) and 0.88, 0.23 cm and 0.17 cm (male, prone), respectively. Manual local adaptations improved the segmentation results significantly (p < 0.01) based on DSC (6.72%) and SD of contour-to-contour distances (0.08 cm) and decreased the 95% confidence intervals of the bladder volume differences. Moreover, expanding the shape model improved the segmentation results significantly (p < 0.01) based on DSC and SD of contour-to-contour distances. CONCLUSIONS: This patient-specific shape model based automatic bladder segmentation method on CBCT is accurate and generic. Our segmentation method only needs two pretreatment imaging data sets as prior knowledge, is independent of patient gender and patient treatment position and has the possibility to manually adapt the segmentation locally.

Spinal cord injury: association with axonal peripheral neuropathy in severely paralysed limbs.

BACKGROUND AND PURPOSE: Pressure sores are a major health problem in spinal cord injury (SCI). In this population pressure damage to peripheral nerves was not thoroughly investigated so far. However, intact peripheral nerves and innervated muscles are a prerequisite for the effectiveness of supportive therapies like functional electrical stimulation (FES). METHODS: We assessed electroneurographic (ENG) data of lower limbs in SCI individuals admitted to our hospital due to severe pressure sores. Our centers prospectively acquired ENG data of the European Multicenter study about SCI (EMSCI) patients served as early control. RESULTS: In the pressure sore cohort (n = 15) all patients were sensory-motor complete (American Spinal Cord Injury Association Impairment Scale A). Most patients (10/15) suffered from a severe axonal sensory-motor polyneuropathy in paralysed legs with absent compound muscle action potentials (CMAPs) of tibial/peroneal nerves as well as absent sensory nerve action potentials of sural nerves. The onset of this polyneuropathy dates within the first year after incident SCI and was mainly associated with increasing sensory-motor completeness as demonstrated by a significant CMAP drop of our centers EMSCI-ENG data on serial tibial nerve recordings in 275 patients. CONCLUSIONS: Severe SCI is associated with an early-onset axonal polyneuropathy in paralysed limbs to which pressure damage might contribute. Because intact peripheral nerves are required for: (i) maintenance of motor function in centrally impaired muscles; and (ii) effectiveness of supportive therapies like FES, ENG-monitoring could serve as a low invasive screening method for peripheral nerve integrity in patients with SCI to initiate pressure relief procedures early enough.

Validation of deformable registration in head and neck cancer using analysis of variance.

PURPOSE: Deformable image registration (DIR) is often validated based on a distance-to-agreement (DTA) criterion of automatically propagated anatomical landmarks that were manually identified. Due to human observer variability, however, the performance of the registration method is diluted. The purpose of this study was to evaluate an analysis of variance (ANOVA) based validation to account for such observer variation. METHODS: Weekly cone beam CTs (CBCTs) of ten head and neck cancer patients undergoing five weeks of radiotherapy were used. An expert identified 23 anatomical features (landmarks) on the planning CT. The landmarks were automatically propagated to the CBCT using multiregion-of-interest (mROI) registration. Additionally, two human observers independently localized these landmarks on the CBCTs. Subsequently, ANOVA was used to compute the variance of each observer on the pairwise distance (PWD). RESULTS: ANOVA based analysis demonstrated that a classical DTA approach underestimated the precision for the mROI due to human observer variation by about 25%. The systematic error (accuracy) of mROI ranged from 0.13 to 0.17 mm; the variability (1 SD) (precision) ranged from 1.3 to 1.5 mm demonstrating that its performance is dominated by the precision. CONCLUSIONS: The PWD-ANOVA method accounts for human observer variation allowing a better estimation of the of DIR errors.

Prognostic significance of radiologically determined neck node volume in head and neck cancer: a systematic review.

This systematic review addresses the prognostic significance of neck node volume in head and neck cancer. Primary tumor volume evolved as an independent significant factor for survival in head and neck cancer patients. Besides primary tumor volume, multiple prognostic features related to the regional lymph nodes were studied in literature. In literature, some authors showed the significance of total tumor volume/nodal volume for survival and loco-regional control. Articles reporting prognosis and survival in nodal tumor volumes were collected by systematically reviewing publications listed in the Pubmed and Embase databases. Publications were included when they at least reported on total tumor volume (TTV) or nodal volume and survival. In this systematic review we studied 21 articles. For measurement of nodal volume different formulas were used. Until now, there's no clear statistical evidence for the use of either TTV or nodal volume versus primary tumor volume to predict the individual loco-regional control or survival after treatment. There is wide variety of tumor measuring systems in the literature. The cut-off value for local tumor response also shows large variation. Firstly consensus should be accomplished on standardization of volume measurements, preferably automatic, and secondly large study groups are needed with identical treatment modalities to further unravel the role of neck node volume as separate staging tool.

Semi-automatic delineation using weighted CT-MRI registered images for radiotherapy of nasopharyngeal cancer.

PURPOSE: To develop a delineation tool that refines physician-drawn contours of the gross tumor volume (GTV) in nasopharynx cancer, using combined pixel value information from x-ray computed tomography (CT) and magnetic resonance imaging (MRI) during delineation. METHODS: Operator-guided delineation assisted by a so-called "snake" algorithm was applied on weighted CT-MRI registered images. The physician delineates a rough tumor contour that is continuously adjusted by the snake algorithm using the underlying image characteristics. The algorithm was evaluated on five nasopharyngeal cancer patients. Different linear weightings CT and MRI were tested as input for the snake algorithm and compared according to contrast and tumor to noise ratio (TNR). The semi-automatic delineation was compared with manual contouring by seven experienced radiation oncologists. RESULTS: A good compromise for TNR and contrast was obtained by weighing CT twice as strong as MRI. The new algorithm did not notably reduce interobserver variability, it did however, reduce the average delineation time by 6 min per case. CONCLUSIONS: The authors developed a user-driven tool for delineation and correction based a snake algorithm and registered weighted CT image and MRI. The algorithm adds morphological information from CT during the delineation on MRI and accelerates the delineation task.

Detection of paroxysmal atrial fibrillation in acute stroke patients.

BACKGROUND: Atrial fibrillation (AF) is a frequent cause of stroke, but detecting paroxysmal AF (pAF) poses a challenge. We investigated whether continuous bedside ECG monitoring in a stroke unit detects pAF more sensitively than 24-hour Holter ECG, and tested whether examining RR interval dynamics on short-term ECG recordings using an automated screening algorithm (ASA) for pAF detection is a useful tool to predict the risk of pAF outside periods of manifest AF. METHODS: Patients >60 years with acute ischemic stroke or transient ischemic attacks (TIA) were prospectively enrolled unless initial ECG revealed AF or they had a history of paroxysmal or persistent AF. ASA was performed on 1- to 2-hour ECG recordings in the emergency room and patients were classified into 5 risk categories for pAF. All patients underwent continuous bedside ECG monitoring for >48 h. Additionally, 24-hour Holter ECG was performed. RESULTS: 136 patients were enrolled (median age: 72 years, male: 58.8%). In 29 (21.3%), pAF was newly diagnosed by continuous bedside ECG monitoring. pAF increased with age (p = 0.031). Median time to first pAF detection on continuous bedside ECG monitoring was 36 h. In 16 patients, pAF was detected by continuous bedside ECG monitoring prior to the performance of 24-hour Holter ECG. Thirteen of the remaining patients were pAF positive on continuous bedside ECG monitoring, but 24-hour Holter detected only 3 patients. Accordingly, the sensitivity of 24-hour Holter was 0.23. Sensitivity of higher-risk categories of ASA compared to continuous bedside ECG monitoring was 0.72, and specificity 0.63. CONCLUSION: Continuous bedside ECG monitoring is more sensitive than 24-hour Holter ECG for pAF detection in acute stroke/TIA patients. Screening patients for pAF outside AF episodes using ASA requires further development.

[Ambiguous swelling of the earlobe]. / Unklare Schwellung des Ohrläppchens.

A 2-year-old girl presented with a reddish swelling of the left earlobe which had been present for over 6 months. Because of the unspecific previous medical history and the unclear clinical symptoms a biopsy of the swelling was carried out. The histological investigation revealed a lymphocyte-infested infiltration with lymph follicles corresponding to cutaneous lymphoid hyperplasia, which is a rare but typical skin manifestation of stage II Lyme borreliosis. The infection could be successfully treated with antibiotics.

Parotid gland sparing IMRT for head and neck cancer improves xerostomia related quality of life.

BACKGROUND AND PURPOSE: To assess the impact of intensity modulated radiotherapy (IMRT) versus conventional radiation on late xerostomia and Quality of Life aspects in head and neck cancer patients. PATIENTS AND NETHODS: Questionnaires on xerostomia in rest and during meals were sent to all patients treated between January 1999 and December 2003 with a T1-4, N0-2 M0 head and neck cancer, with parotid gland sparing IMRT or conventional bilateral neck irradiation to a dose of at least 60 Gy, who were progression free and had no disseminated disease (n = 192). Overall response was 85% (n = 163); 97% in the IMRT group (n = 75) and 77% in the control group (n = 88) the median follow-up was 2.6 years. The prevalence of complaints was compared between the two groups, correcting for all relevant factors at multivariate ordinal regression analysis. RESULTS: Patients treated with IMRT reported significantly less difficulty transporting and swallowing their food and needed less water for a dry mouth during day, night and meals. They also experienced fewer problems with speech and eating in public. Laryngeal cancer patients in general had fewer complaints than oropharynx cancer patients but both groups benefited from IMRT. Within the IMRT group the xerostomia scores were better for those patients with a mean parotid dose to the "spared" parotid below 26 Gy. CONCLUSION: Parotid gland sparing IMRT for head and neck cancer patients improves xerostomia related quality of life compared to conventional radiation both in rest and during meals. Laryngeal cancer patients had fewer complaints but benefited equally compared to oropharyngeal cancer patients from IMRT.

Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumor.

PURPOSE: In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated. METHODS: Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor. RESULTS: Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. CONCLUSIONS: In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were significantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy.