Novel hybrid treatment planning approach for irradiation a pediatric craniospinal axis.

This study presents a new treatment planning approach merging 3D-CRT and VMAT fields into a hybrid treatment plan (HybTP), in order to achieve an optimum dose coverage of the planning target volume (PTV) and protection of OAR. Craniospinal axis irradiation (CSI) treated with 3D conformal radiotherapy (3D-CRT) is associated with high doses to the heart and eye lenses but provides better sparing of lungs and kidneys compared to volumetric modulated arc therapy (VMAT). VMAT treatment spares eye lenses and the heart, but lungs and kidneys are not as effective as 3D-CRT. Thus, a combination of both techniques (HybTP) may be optimal in sparing all these organs at risk (OAR). The results of HybTP are compared with helical tomotherapy (HT), intensity modulated radio therapy (IMRT), VMAT, and 3D-CRT plans. Hybrid, HT, VMAT, IMRT, and 3D-CRT treatment plans for a male child (age 6 years) with medulloblastoma were created and compared. A total dose of 35.2 Gy (PTV) with a dose per fraction of 1.6 Gy was prescribed. The following dose acceptance criteria were defined: The plans were compared regarding dose homogeneity index (HI) and conformity index (CI), PTV coverage, (particularly at cribriform plate) and doses at OARs. Best conformity was achieved with HT (CI = 0.98) followed by VMAT (CI = 0.96), IMRT (CI = 0.91), HybTP (CI = 0.86), and 3D-CRT (CI = 0.83). The homogeneity index varied marginally. For both HT and IMRT the HI was 0.07, and for 3D-CRT, VMAT and HybTP the HI was between 0.13 and 0.15. The cribriform plate was sufficiently covered by HybTP, VMAT, and 3D-CRT. The dose acceptance criteria for OARs were met by HT and HybTP. VMAT did not meet the criteria for lung (Dmean = right 10.4 Gy/left 10.2 Gy), 3D-CRT did not meet the criteria for eye lenses (Dmax = right 32.3 Gy/left 33.1), and heart (V25≈44%) and IMRT did not meet the criteria for lung (Dmean = right 11.1 Gy/left 11.2 Gy) and eye lenses (Dmax = right 12.2 Gy/left 13.1). HybTP meets all defined acceptance criteria and has proved to be a reasonable alternative for CSI. With HybTP that combines VMAT at the brain and heart with 3D-CRT posterior spinal fields (to spare lungs and kidneys), both appropriate coverage of the PTV and sparing of OAR can be achieved.

Relationship between reticular pH parameters and potential on-farm indicators in the early lactation of dairy cows.

Subacute ruminal acidosis (SARA) is an important nutritional disorder affecting animal welfare and economy of milk production. Definitions rely on ruminal pH but due to limitations of its measurement, indicators reflecting low pH are highly desirable. The aim of this study was to investigate the relationship between reticular pH and 18 on-farm indicators in milk, blood, faeces, urine and chewing behaviour in early lactating dairy cows. Ten farms were visited for 3 weeks and in total samples of 100 cows (10 per farm) were taken. The statistics and graphical visualization were performed using Pearson correlation and linear regression models on an animal individual level as well as with linear mixed models. Eight indicators (milk fat, fat-to-protein ratio, rumination time, feed intake time, rumination frequency, rumination boluses, lying time and faecal pH) were statistically significant associated with the daily animal individual reticular pH average. However, none of the models including the potential explanatory variables explained more than 5% of the pH variations. The study confirms the necessity of pH measurement to detect SARA risk animals in early lactation dairy cows.

Planning Benchmark Study for Stereotactic Body Radiation Therapy of Liver Metastases: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

PURPOSE: Our purpose was to investigate whether liver stereotactic body radiation therapy treatment planning can be harmonized across different treatment planning systems, delivery techniques, and institutions by using a specific prescription method and to minimize the knowledge gap concerning intersystem and interuser differences. We provide best practice guidelines for all used techniques. METHODS AND MATERIALS: A multiparametric specification of target dose (gross target volume [GTV]D50%, GTVD0.1cc, GTVV90%, planning target volume [PTV]V70%) with a prescription dose of GTVD50% = 3 × 20 Gy and organ-at-risk (OAR) limits were distributed with computed tomography and structure sets from 3 patients with liver metastases. Thirty-five institutions provided 132 treatment plans using different irradiation techniques. These plans were first analyzed for target and OAR doses. Four different renormalization methods were performed (PTVDmin, PTVD98%, PTVD2%, PTVDmax). The resulting 660 treatments plans were evaluated regarding target doses to study the effect of dose renormalization to different prescription methods. A relative scoring system was used for comparisons. RESULTS: GTVD50% prescription can be performed in all systems. Treatment plan harmonization was overall successful, with standard deviations for Dmax, PTVD98%, GTVD98%, and PTVDmean of 1.6, 3.3, 1.9, and 1.5 Gy, respectively. Primary analysis showed 55 major deviations from clinical goals in 132 plans, whereas in only <20% of deviations GTV/PTV dose was traded for meeting OAR limits. GTVD50% prescription produced the smallest deviation from target planning objectives and between techniques, followed by the PTVDmax, PTVD98%, PTVD2%, and PTVDmin prescription. Deviations were significant for all combinations but for the PTVDmax prescription compared with GTVD50% and PTVD98%. Based on the various dose prescription methods, all systems significantly differed from each other, whereas GTVD50% and PTVD98% prescription showed the least difference between the systems. CONCLUSIONS: This study showed the feasibility of harmonizing liver stereotactic body radiation therapy treatment plans across different treatment planning systems and delivery techniques when a sufficient set of clinical goals is given.

Comparative analysis between interstitial brachytherapy and stereotactic body irradiation for local ablation in liver malignancies.

PURPOSE: Interstitial high-dose-rate brachytherapy (BT) is an alternative treatment option to stereotactic body radiotherapy (SBRT) for the ablative treatment of liver malignancies. The aim of the present comparative planning study was to reveal the possibilities and limitations of both techniques with regard to dosimetric properties. METHODS AND MATERIALS: Eighty-five consecutive patients with liver malignancy diagnosis were treated with interstitial BT between 12/2008 and 09/2009. The prescription dose of BT varied between 15 and 20 Gy, depending on histology. For dosimetric comparison, virtual SBRT treatment plans were generated using the original BT planning CTs. Additional margins reflecting the respiratory tumor motion were added to the target volumes for SBRT planning. RESULTS: The mean PTVBT was 34.7 cm3 (0.5-410.0 cm3) vs. a mean PTVSBRT of 73.2 cm3 (6.1-593.4 cm3). Regarding the minimum peripheral dose (D99.9), BT achieved the targeted prescription dose of 15 Gy/20 Gy better without violating organ at risk constraints. The dose exposure of the liver was significantly influenced by treatment modality. The liver exposure to 5 Gy was statistically lower with 611 ± 43 cm3 for BT as compared with 694 ± 37 cm3 for SBRT plans (20-Gy group, p = 0.001), corresponding to 41.8% vs. 45.9% liver volume, respectively. CONCLUSIONS: To the best of our knowledge, this is the first report on the comparison of clinically treated liver BT treatments with virtually planned SBRT treatments. The planning study showed a superior outcome of BT regarding dose coverage of the target volume and exposed liver volume. Nevertheless, further studies are needed to determine ideal applicability for each treatment approach.

Results of a multicenter intensity modulated radiation therapy treatment planning comparison study for a sample prostate cancer case.

PURPOSE: To determine the influence of different medical physicists, photon energies, treatment planning systems and treatment machines on the resulting external beam radiotherapy dose distribution for a sample prostate cancer case. METHODS: A pre-contoured computed tomography (CT) dataset containing planning target volume 1 (PTV1) prostate and seminal vesicles (single dose [SD] 1.8 Gy, total dose [TD] 59.4 Gy), PTV2 prostate (simultaneously integrated boost [SIB], SD 2.0 Gy, TD 66 Gy), PTV3 prostate and seminal vesicles approach (SD 1.8 Gy, TD 73.8 Gy/80.4 Gy SIB) as well as organs at risk (OAR: rectum, bladder, femoral heads, bowel, anus) was offered to the members of the task group IMRT (intensity-modulated radiation therapy) of the German Society for Medical Physics. The purpose was to calculate one combined treatment plan (TP) for PTV1 and PTV2, as well as a separate one for PTV3. Dose volume histograms (DVH), different dose values, conformity index (CI), homogeneity index (HI), gradient index (GI) and a new "better than average score" were used to analyse the dose distributions. RESULTS: Altogether 44 institutions took part in this study and submitted acceptable dose distributions for the PTVs. However, there were statistically significant differences, especially for the doses administered to the OAR, such as rectum, bladder and femoral heads. Differences between the treatment plans were not easily detectable by visual inspection of the isodose distribution. Dose maxima may occur outside the PTV. Even though scoring indices are already published, the new "better than average score" was needed to identify a plan that minimises dose to all OAR simultaneously. CONCLUSION: Different medical physicists or dosimetrists, photon energies, treatment planning systems, and treatment machines have an impact on the resulting dose distribution. However, the differences only become apparent when comparing DVH, analysing dose values, comparing CI, HI, GI, as well as reviewing the dose distribution in every single plane. A new score was introduced to identify treatment plans that simultaneously deliver a low dose to all OAR. Such inter- and intra-institutional comparison studies are needed to explore different treatment planning strategies; however, there is still no automatic solution for an "optimal" treatment plan.

Does access to pasture affect claw condition and health in dairy cows?

The aim of this study was to examine effects of pasturing in dairy cows on claw condition (claw length, hardness) and on the prevalence of claw diseases. At claw trimming, a total of 240 Holstein-Friesian or Red-Holstein cows from 20 German farms were examined twice, at the end of the pasture and barn season. Each individual claw was trimmed at both assessments. Farms were classified based on animals' pasture access during pasture season into: group 1 (G1) >10 hours pasture access per day, group 2 (G2) 6-10 hours, group 3 (G3) <6 hours and group 4 (G4) without pasture access. Greater values for hardness were associated with lower scores (=prevalence×severity level) of sole ulcers, white line disease, sole haemorrhage, heel horn erosion and interdigital hyperplasia. In pasture groups, heel horn erosion showed lower frequencies in summer compared with winter, while it was vice versa in G4. In G1 and G3, lower frequencies of white line disease were found in summer compared with winter. Overall, pasture access had positive effects in particular for claw diseases that are related to moist environments. Nevertheless, appropriate free-stall design and claw trimming routine might have a greater influence.

Towards accurate dose accumulation for Step-&-Shoot IMRT: Impact of weighting schemes and temporal image resolution on the estimation of dosimetric motion effects.

PURPOSE: Breathing-induced motion effects on dose distributions in radiotherapy can be analyzed using 4D CT image sequences and registration-based dose accumulation techniques. Often simplifying assumptions are made during accumulation. In this paper, we study the dosimetric impact of two aspects which may be especially critical for IMRT treatment: the weighting scheme for the dose contributions of IMRT segments at different breathing phases and the temporal resolution of 4D CT images applied for dose accumulation. METHODS: Based on a continuous problem formulation a patient- and plan-specific scheme for weighting segment dose contributions at different breathing phases is derived for use in step-&-shoot IMRT dose accumulation. Using 4D CT data sets and treatment plans for 5 lung tumor patients, dosimetric motion effects as estimated by the derived scheme are compared to effects resulting from a common equal weighting approach. Effects of reducing the temporal image resolution are evaluated for the same patients and both weighting schemes. RESULTS: The equal weighting approach underestimates dosimetric motion effects when considering single treatment fractions. Especially interplay effects (relative misplacement of segments due to respiratory tumor motion) for IMRT segments with only a few monitor units are insufficiently represented (local point differences >25% of the prescribed dose for larger tumor motion). The effects, however, tend to be averaged out over the entire treatment course. Regarding temporal image resolution, estimated motion effects in terms of measures of the CTV dose coverage are barely affected (in comparison to the full resolution) when using only half of the original resolution and equal weighting. In contrast, occurence and impact of interplay effects are poorly captured for some cases (large tumor motion, undersized PTV margin) for a resolution of 10/14 phases and the more accurate patient- and plan-specific dose accumulation scheme. CONCLUSIONS: Radiobiological consequences of reported single fraction local point differences >25% of the prescribed dose are widely unclear and should be subject to future investigation. Meanwhile, if aiming at accurate and reliable estimation of dosimetric motion effects, precise weighting schemes such as the presented patient- and plan-specific scheme for step-&-shoot IMRT and full available temporal 4D CT image resolution should be applied for IMRT dose accumulation.

Comparison of electron IMRT to helical photon IMRT and conventional photon irradiation for treatment of breast and chest wall tumours.

BACKGROUND AND PURPOSE: Conventional irradiation of breast and chest wall tumours may cause high doses in underlying organs. Intensity-modulated radiation therapy (IMRT) with photons achieves high conformity between treated and tumour volume but is associated with considerable low-dose effects which may induce secondary malignancies. We compare treatment plans of electron IMRT to helical photon IMRT and conventional irradiation. MATERIAL AND METHODS: Treatment planning for three patients (breast, chest wall plus lymph nodes, sarcoma of medial chest wall/sternum) was performed using XiO 4.3.3 (CMS) for conventional photon irradiation, Hi-Art 2.2.2.05 (TomoTherapy) for helical photon IMRT, and a self-designed programme for electron IMRT. RESULTS: The techniques resulted in similar mean and maximum target doses. Target coverage by the 95%-isodose was best with tomotherapy. Mean ipsilateral lung doses were similar with all techniques. Electron IMRT achieved best sparing of heart, and contralateral breast. Compared with photon IMRT, electron IMRT allowed better sparing of contralateral lung and total healthy tissue. CONCLUSIONS: Electron IMRT is superior to conventional irradiation, as it allows satisfying target coverage and avoids high doses in underlying organs. Its advantage over photon IMRT is better sparing of most organs at risk (low-dose effects) which reduces the risk of radiation-induced malignancies.

Evaluation of prognostic factors and two radiation techniques in patients treated with surgery followed by radio(chemo)therapy or definitive radio(chemo)therapy for locally advanced head-and-neck cancer.

BACKGROUND AND PURPOSE: Conventional radiotherapy (RT) still is the standard technique for head-and-neck cancer in many centers worldwide, whereas other centers replaced this technique by 3-D conformal RT, which is associated with more appropriate dose distributions. Comparative studies regarding outcome and toxicity are lacking. This study compared both techniques for overall survival (OS), metastases-free survival (MFS), loco-regional control (LC), and toxicity in stage III/IV head-and-neck cancer. PATIENTS AND METHODS: Data of 345 patients irradiated for stage III/IV squamous cell head-and-neck cancer were retrospectively analyzed. Patients received conventional RT (group A, n = 166) or 3-D conformal RT (group B, n = 179). Both techniques were compared for outcomes and toxicity. Eleven further potential prognostic factors were investigated: age, gender, performance status, tumor site, grading, T-stage, N-stage, AJCC-stage, chemotherapy, surgery, pre-RT hemoglobin. RESULTS: 3-year-OS was 62% in group A and 57% in group B (p = 0.15). 3-year-MFS was 67% and 76% (p = 0.46), 3-year-LC was 65% and 68%, respectively (p = 0.71). On multivariate analysis, gender (p = 0.005), performance status (p < 0.001), T-stage (p = 0.002), and N-stage (p < 0.001) were associated with OS. MFS was influenced by performance status (p < 0.001) and N-stage (p < 0.001), LC by gender (p = 0.021), T-stage (p < 0.001), and pre-RT hemoglobin level (>or= 12 better than < 12 g/dl, p = 0.004). Grade 2-3 xerostomia was less frequent with 3-D conformal RT (43% vs. 58%, p = 0.06). Otherwise, toxicities were similar. CONCLUSION: Both RT techniques resulted in similar treatment outcomes. Because xerostomia was less with 3-D conformal RT, this technique appeared beneficial for patients, in whom one parotid gland can be spared. Outcome was associated with gender, performance status, tumor stage, and pre-RT hemoglobin.

High accuracy of virtual simulation with the laser system Dorado CT4.

PURPOSE: To evaluate the accuracy of virtual simulation, which is less time-consuming than physical simulation, with the new laser system Dorado CT4 in 96 prostate cancer patients. PATIENTS AND METHODS: Virtual simulation was based on a spiral scan with 8 mm reconstruction index and 8 mm slice thickness in 64 patients (group A), and 3 mm reconstruction index and 3 mm slice thickness in 32 patients (group B). Both groups were evaluated for impact on maximum difference (Deltamax) regarding the isocenters obtained from virtual simulation versus those obtained from physical simulation. RESULTS: In the entire cohort, mean differences were as follows: Deltamax 5.7 +/- 3.5 mm, Deltax (left/right) 2.8 +/- 2.9 mm, Deltay (anterior/posterior) 4.5 +/- 3.8 mm, and Deltaz (cranial/caudal) 2.1 +/- 2.2 mm. In group A, mean values were Deltamax 6.2 +/- 3.8 mm, Deltax 2.9 +/- 3.1 mm, Deltay 4.9 +/- 4.2 mm, and Deltaz 2.3 +/- 2.3 mm. In group B, mean values were Deltamax 4.8 +/- 2.8 mm, Deltax 2.7 +/- 2.7 mm, Deltay 3.7 +/- 2.7 mm, and Deltaz 1.7 +/- 2.0 mm. Time of radiotherapy (primary vs. salvage RT) and radiation regimen (external-beam radiotherapy [EBRT] vs. high-dose-rate brachytherapy [HDR-BT] plus EBRT) had no significant impact on Deltamax. CONCLUSION: Virtual simulation with the new laser system Dorado CT4 was very precise for both primary and salvage RT in the treatment of prostate cancer patients. High precision was achieved for both EBRT and HDR-BT plus EBRT. Virtual simulation should be performed with a planning CT with 3 mm reconstruction index and 3 mm slice thickness for high accuracy.

On the dosimetric behaviour of photon dose calculation algorithms in the presence of simple geometric heterogeneities: comparison with Monte Carlo calculations.

A comparative study was performed to reveal differences and relative figures of merit of seven different calculation algorithms for photon beams when applied to inhomogeneous media. The following algorithms were investigated: Varian Eclipse: the anisotropic analytical algorithm, and the pencil beam with modified Batho correction; Nucletron Helax-TMS: the collapsed cone and the pencil beam with equivalent path length correction; CMS XiO: the multigrid superposition and the fast Fourier transform convolution; Philips Pinnacle: the collapsed cone. Monte Carlo simulations (MC) performed with the EGSnrc codes BEAMnrc and DOSxyznrc from NRCC in Ottawa were used as a benchmark. The study was carried out in simple geometrical water phantoms (rho = 1.00 g cm(-3)) with inserts of different densities simulating light lung tissue (rho = 0.035 g cm(-3)), normal lung (rho = 0.20 g cm(-3)) and cortical bone tissue (rho = 1.80 g cm(-3)). Experiments were performed for low- and high-energy photon beams (6 and 15 MV) and for square (13 x 13 cm2) and elongated rectangular (2.8 x 13 cm2) fields. Analysis was carried out on the basis of depth dose curves and transverse profiles at several depths. Assuming the MC data as reference, gamma index analysis was carried out distinguishing between regions inside the non-water inserts or inside the uniform water. For this study, a distance to agreement was set to 3 mm while the dose difference varied from 2% to 10%. In general all algorithms based on pencil-beam convolutions showed a systematic deficiency in managing the presence of heterogeneous media. In contrast, complicated patterns were observed for the advanced algorithms with significant discrepancies observed between algorithms in the lighter materials (rho = 0.035 g cm(-3)), enhanced for the most energetic beam. For denser, and more clinical, densities a better agreement among the sophisticated algorithms with respect to MC was observed.

Prognostic factors in head-and-neck cancer patients treated with surgery followed by intensity-modulated radiotherapy (IMRT), 3D-conformal radiotherapy, or conventional radiotherapy.

In 148 head-and-neck cancer patients treated with surgery plus radiotherapy (RT), IMRT, 3D-conformal RT, and conventional RT and 10 potential prognostic factors were evaluated for overall survival (OS), metastasis-free survival (MFS), and loco-regional control (LC). On univariate analysis, ECOG performance status, T-stage, AJCC-stage, extent of resection, and pre-RT hemoglobin level (>or=12 g/dl better than <12 g/dl) were significantly associated with treatment outcome, whereas RT technique had no significant impact. On multivariate analysis, performance status maintained significance for OS (P=0.019), AJCC-stage for LC (P=0.034), extent of resection for OS (P=0.045) and MFS (P=0.021), pre-RT hemoglobin for MFS (P<0.001). IMRT was associated with less xerostomia than conformal RT and conventional RT (17% versus 63% and 73%, P=0.037). Otherwise, acute and late toxicity was similar. Outcome was significantly associated with performance status, tumor stage, extent of resection, and pre-RT hemoglobin. The three radiation techniques provided similar disease control. IMRT was effective in significantly reducing xerostomia.

Comparison of dose calculation algorithms for treatment planning in external photon beam therapy for clinical situations.

A study of the performance of five commercial radiotherapy treatment planning systems (TPSs) for common treatment sites regarding their ability to model heterogeneities and scattered photons has been performed. The comparison was based on CT information for prostate, head and neck, breast and lung cancer cases. The TPSs were installed locally at different institutions and commissioned for clinical use based on local procedures. For the evaluation, beam qualities as identical as possible were used: low energy (6 MV) and high energy (15 or 18 MV) x-rays. All relevant anatomical structures were outlined and simple treatment plans were set up. Images, structures and plans were exported, anonymized and distributed to the participating institutions using the DICOM protocol. The plans were then re-calculated locally and exported back for evaluation. The TPSs cover dose calculation techniques from correction-based equivalent path length algorithms to model-based algorithms. These were divided into two groups based on how changes in electron transport are accounted for ((a) not considered and (b) considered). Increasing the complexity from the relatively homogeneous pelvic region to the very inhomogeneous lung region resulted in less accurate dose distributions. Improvements in the calculated dose have been shown when models consider volume scatter and changes in electron transport, especially when the extension of the irradiated volume was limited and when low densities were present in or adjacent to the fields. A Monte Carlo calculated algorithm input data set and a benchmark set for a virtual linear accelerator have been produced which have facilitated the analysis and interpretation of the results. The more sophisticated models in the type b group exhibit changes in both absorbed dose and its distribution which are congruent with the simulations performed by Monte Carlo-based virtual accelerator.