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.

Toxicity and risk factors after combined high-dose-rate brachytherapy and external beam radiation therapy in men ≥75 years with localized prostate cancer.

PURPOSE: Combined high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) is a favorable treatment option in non-metastatic prostate cancer. However, reports on toxicity and outcome have mainly focused on younger patients. We aimed to determine toxicity and biochemical control rates after combined HDR-BT and EBRT in men ≥75 years. METHODS: From 1999 to 2015, 134 patients aged ≥75 years (median 76 years; 75-82 years) were identified. Patients received 18 Gy of HDR-BT (9 Gy/fraction on days 1 and 8) with an iridium-192 source. After 1 week, supplemental EBRT with a target dose of 50.4 Gy was started (delivered in 1.8 Gy fractions). RESULTS: Median follow-up time was 25 months (0-127 months). No severe (grade 4) gastrointestinal (GIT) or genitourinary (GUT) toxicities were observed. In 76 patients (56.7%), 3D conformal radiation therapy (CRT) and in 34.3% intensity-modulated radiotherapy (IMRT) was applied. CRT-treated patients were at a 2.17-times higher risk (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.31-3.57, p = 0.002) of experiencing GUT. GIT risks could be reduced by 78% using IMRT (HR: 0.22, 95% CI: 0.07-0.75, p = 0.015). Patients with a higher T stage (T2c-3a/b) were less likely to experience GIT or GUT (HR: 0.49, 95% CI: 0.29-0.85, p = 0.011 and HR: 0.5, 95% CI: 0.3-0.81, p = 0.005, respectively). CONCLUSION: HDR-BT/EBRT is a well-tolerated treatment option for elderly men ≥75 years with a limited number of comorbidities and localized intermediate- or high-risk prostate cancer. IMRT should be favored since side effects were significantly reduced in IMRT-treated patients.

The impact of [68Ga]PSMA I&T PET/CT on radiotherapy planning in patients with prostate cancer.

PURPOSE: To determine the impact of Gallium-68-labled prostate-specific membrane antigen positron-emission tomography/computed tomography ([68Ga]PSMA PET/CT) on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer. METHODS: A total of 106 patients with prostate cancer scheduled for radiation therapy underwent 120 [68Ga]PSMA PET/CT scans prior to radiotherapy treatment. In 20 cases, patients underwent [68Ga]PSMA PET/CT for primary therapy (PT), 75 cases were referred for biochemical relapse after surgery (RL), and 25 cases were intended for palliative treatment of localized metastases (MD). We retrospectively compared the impact of [68Ga]PSMA PET/CT on lesion detection and treatment decision to CT alone. RESULTS: [68Ga]PSMA PET/CT revealed a total of 271 positive lesions, whereas CT detected 86 lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases (46%) based on the higher detection rate of [68Ga]PSMA PET/CT: in 15% of cases with PT, in 43% of cases with RL, and in 44% of cases with MD. CONCLUSION: [68Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate cancer, thereby significantly impacting on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [68Ga]PSMA I&T and comparison with published data of [68Ga]PSMA HBED-CC.

PURPOSE: To determine the detection rate of PET/CT in biochemical relapse of prostate cancer using [68Ga]PSMA I&T and to compare it with published detection rates of [68Ga]PSMA HBED-CC. METHODS: We performed a retrospective analysis in 83 consecutive patients with documented biochemical relapse after prostatectomy. All patients underwent whole body [68Ga]PSMA I&T PET/CT. PET/CT images were evaluated for presence of local recurrence, lymph node metastases, and distant metastases. Proportions of positive PET/CT results were calculated for six subgroups with increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, ≥10.0 ng/mL). Detection rates of [68Ga]PSMA I&T were statistically compared with published detection rates of [68Ga]PSMA HBED-CC using exact Fisher's test. RESULTS: Median PSA was 0.81 (range: 0.01 - 128) ng/mL. In 58/83 patients (70 %) at least one [68Ga]PSMA I&T positive lesion was detected. Local recurrent cancer was present in 18 patients (22 %), lymph node metastases in 29 patients (35 %), and distant metastases in 15 patients (18 %). The tumor detection rate was positively correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55 % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 % (5.0 to <10.0 ng/mL), and 100 % (≥10.0 ng/mL). There was no significant difference between the detection rate of [68Ga]PSMA I&T and published detection rates of [68Ga]PSMA HBED-CC (all p>0.05). CONCLUSIONS: [68Ga]PSMA I&T PET/CT has high detection rates of recurrent prostate cancer that are comparable to [68Ga]PSMA HBED-CC.

The use of IMRT in Germany.

BACKGROUND: Intensity modulated radiotherapy (IMRT) is frequently used, but there are no data about current frequency regarding specific tumor sites and equipment used for quality assurance (QA). MATERIALS AND METHODS: An online survey about IMRT was executed from April to October 2014 by the collaborative IMRT working group (AK IMRT) of the German Association of Medical Physicists (DGMP). RESULTS: A total of 23 German institutions took part in the survey. Most reports came from users working with Elekta, Varian, and Siemens treatment machines, but also from TomoTherapy and BrainLab. Most frequent IMRT technology was volumetric modulated arc therapy (58.37 %: VMAT/"rapid arc"), followed by step-and-shoot IMRT (14.66 %), dynamic MLC (dMLC: 14.53 %), TomoTherapy (9.25 %), and 3.2 % other techniques. Different commercial hard- and software solutions are available for QA, whereas many institutes still develop their own phantoms. Data of 26,779 patients were included in the survey; 44 % were treated using IMRT techniques. IMRT was most frequently used for anal cancer, (whole) craniospinal irradiation, head and neck cancer, prostate cancer, other tumors in the pelvic region, gynecological tumors (except for breast cancer), and brain tumors. DISCUSSION: An estimated 10 % of all patients treated in 2014 with radiation in Germany were included in the survey. It is representative for the members of the AK IMRT. CONCLUSION: IMRT may be on the way to replace other treatment techniques. However, many scientific questions are still open. In particular, it is unclear when the IMRT technique should not be used.

Late recurrence of a pineal germinoma 14 years after radiation and chemotherapy: a case report and review of the literature.

BACKGROUND: Intracranial germinomas (IG) are rare and highly curable tumors. The incidence and optimal treatment of recurrences are not well defined. CASE REPORT: A 34-year-old male was diagnosed with a late recurrence of an IG 14 years after the initial diagnosis and treatment. The diagnosis was complicated by the absence of tumor markers and delayed histological sampling of the lesion. Upon histological confirmation, the patient received 2 cycles of conventional chemotherapy, followed by 2 cycles of highdose chemotherapy and peripheral blood stem cell transplantation. The patient achieved a complete remission on magnetic resonance imaging scan. Consolidating radiation of the involved field was performed after termination of the chemotherapy. CONCLUSION: Limited information on the optimal management of late relapses of IG call for individualized therapeutic approaches. Platinum-based chemotherapy, followed by high-dose chemotherapy and consolidative radiation, appears to be feasible and effective in this situation.

Development and characterization of modular mouse phantoms for end-to-end testing and training in radiobiology experiments.

Objective. In radiation oncology, experiments are often carried out using mice as a model forin vivoresearch studies. Due to recent technological advances in the development of high-precision small-animal irradiation facilities, the importance of quality assurance for both dosimetry and imaging is increasing. Additive manufacturing (AM) offers the possibility to produce complex models from a three-dimensional data set and to build cost-effective phantoms that can easily be adapted to different purposes. The aim of this work was therefore to develop detailed anatomical mouse models for quality assurance and end-to-end testing of small-animal irradiation and imaging by means of AM.Approach. Two mouse phantom concepts were designed, constructed, and examined for this purpose. The first model includes cavities corresponding to the most important organs. The final solid model was constructed using AM in two separate parts that can be attached with a plug connection after filling these cavities with tissue-equivalent mixtures. Moreover, different radiation dosimeters can be placed in the lower part of the model. For the second concept, AM was used for building modules like the phantom outer shell and bones, so that different mixtures can be used as a filling, without modifying the phantom structure.Main results.CT as well as Micro-CT scans of both concepts showed an excellent quality and adequate image contrast, with material attenuation properties close to those of mouse tissues, apart from the current bone surrogates. Radiation dose measurements with radiochromic films were, with some exceptions in areas with larges bone volumes, in agreement with calculations within less than ±4%.Significance. AM shows great potential for the development of mouse models that are inexpensive, easy to adapt, and accurate, thus enabling their use for quality assurance in small-animal radiotherapy and imaging. The introduction of such 3D-printable mouse phantoms in the workflow could also significantly reduce the use of living animals for optimization and testing of new imaging and irradiation protocols.

Radiosensitisation and enhanced tumour growth delay of colorectal cancer cells by sustained treatment with trifluridine/tipiracil and X-rays.

Trifluridine/tipiracil (FTD/TPI; marketed as Lonsurf®) has shown clinically relevant activity after fluoropyrimidine failure in colorectal cancer and may thus be of increased efficacy compared with current standard capecitabine chemoradiation. Here we investigated the colorectal cancer cell lines HT29, HCT116, SW48 and Caco-2 to provide a preclinical rationale for FTD/TPI-based chemoradiation treatment. All lines incorporated similar amounts of FTD, irrespective of treatment concentration and duration, then arrested in S phase, showed persistent γH2AX induction and eventually underwent endoreplication, resulting in polyploidy. Clonogenic assays performed for four combined treatment schedules demonstrated additivity for treatments given within 6 h of each other. However, 24 h FTD/TPI treatment prior to irradiation caused 1.6-2.4 fold radiosensitisation. Combined in vivo treatment was well tolerated and caused a marked tumour growth delay, similar to capecitabine radiochemotherapy regimes. Prolonged S phase arrest, persistent γH2AX signalling, endoreplication and polyploidy may contribute to the cytotoxicity of FTD/TPI. The strong radiosensitising effect observed in vitro after prolonged treatment with FTD/TPI and equivalence with capecitabine-based chemoradiation in vivo support a daily fractionated combined regime of FTD/TPI and radiation in rectal cancer treatment. This is now being tested in a phase I/II clinical trial (NCT04177602).

Modeling Growth of Tumors and Their Spreading Behavior Using Mathematical Functions.

Computer simulations of the spread of malignant tumor cells in an entire organism provide important insights into the mechanisms of metastatic progression. Key elements for the usefulness of these models are the adequate selection of appropriate mathematical models describing the tumor growth and its parametrization as well as a proper choice of the fractal dimension of the blood vessels in the primary tumor. In addition, survival in the bloodstream and evasion into the connective spaces of the target organ of the future metastasis have to be modeled. Determination of these from experimental models is complicated by systematic and unsystematic experimental errors which are difficult to assess. In this chapter, we demonstrate how to select the best-suited mathematical function to describe tumor growth for experimental xenograft mouse tumor models and how to parametrize them. Common pitfalls and problems are described as well as methods to avoid them.

Locally Ablative Radiation Therapy of a Primary Human Small Cell Lung Cancer Tumor Decreases the Number of Spontaneous Metastases in Two Xenograft Models.

PURPOSE: To investigated the influence of radiation therapy (RT), surgery (OP), radio-chemotherapy (RChT), or chemotherapy (ChT) on small cell lung cancer metastases in 2 xenograft models. METHODS AND MATERIALS: A total of 1 × 106 human small cell lung cancer cells (OH1, H69) were subcutaneously injected into severe combined immunodeficiency mice to form a local primary tumor node at the lower trunk. Radiation therapy, OP, RChT, or ChT were started after development of palpable tumors. Chemotherapy was given as a single intraperitoneal injection of cisplatin. Radiation therapy was 5 × 10 Gy on the local tumor node. Two additional groups were implemented to assess primary tumors and distant metastases in untreated mice at the beginning (control group A) and at the end of the experiment (control group B). Proapoptotic, antiproliferative, antiangiogenic, and hypoxic effects were assessed by Feulgen, Ki67, S1P1 receptor, and hypoxia-inducible factor 1α staining, respectively. Quantitative Alu-polymerase chain reaction was used to determine circulating tumor cells in the blood, and disseminated tumor cells in the lungs, bone marrow, liver, and brain. RESULTS: In both xenograft models, RT and RChT abrogated local tumor growth, indicated by increased apoptosis, decreased cell proliferation, and reduced microvessel density (equally affecting vessels of all diameters). Regarding metastases, RT and RChT not only counteracted the time-dependent increase of dissemination but also decreased the metastatic load pre-existing at therapy induction in the blood, lungs, and liver. Only in the case of relapse-free surgery could similar effects be achieved by OP. CONCLUSIONS: Our models provide evidence that RT and RChT ablate the primary tumor and inhibit metastasis development over time. Upon local recurrence, RT showed beneficial effects compared with OP with regard to suppression of circulating tumor cells and disseminated tumor cells.

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.

An optical flow based method for improved reconstruction of 4D CT data sets acquired during free breathing.

Respiratory motion degrades anatomic position reproducibility and leads to issues affecting image acquisition, treatment planning, and radiation delivery. Four-dimensional (4D) computer tomography (CT) image acquisition can be used to measure the impact of organ motion and to explicitly account for respiratory motion during treatment planning and radiation delivery. Modern CT scanners can only scan a limited region of the body simultaneously and patients have to be scanned in segments consisting of multiple slices. A respiratory signal (spirometer signal or surface tracking) is used to reconstruct a 4D data set by sorting the CT scans according to the couch position and signal coherence with predefined respiratory phases. But artifacts can occur if there are no acquired data segments for exactly the same respiratory state for all couch positions. These artifacts are caused by device-dependent limitations of gantry rotation, image reconstruction times and by the variability of the patient's respiratory pattern. In this paper an optical flow based method for improved reconstruction of 4D CT data sets from multislice CT scans is presented. The optical flow between scans at neighboring respiratory states is estimated by a non-linear registration method. The calculated velocity field is then used to reconstruct a 4D CT data set by interpolating data at exactly the predefined respiratory phase. Our reconstruction method is compared with the usually used reconstruction based on amplitude sorting. The procedures described were applied to reconstruct 4D CT data sets for four cancer patients and a qualitative and quantitative evaluation of the optical flow based reconstruction method was performed. Evaluation results show a relevant reduction of reconstruction artifacts by our technique. The reconstructed 4D data sets were used to quantify organ displacements and to visualize the abdominothoracic organ motion.

Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

BACKGROUND: Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities. METHODS: The biological data gained during these experiments were fed into our previously developed computer model "Cancer and Treatment Simulation Tool" (CaTSiT) to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model. RESULTS: According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels' geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor's therapeutic susceptibility and its metastatic spreading behavior. CONCLUSION: Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

Magnetic resonance imaging for precise radiotherapy of small laboratory animals.

AIMS: Radiotherapy of small laboratory animals (SLA) is often not as precisely applied as in humans. Here we describe the use of a dedicated SLA magnetic resonance imaging (MRI) scanner for precise tumor volumetry, radiotherapy treatment planning, and diagnostic imaging in order to make the experiments more accurate. METHODS AND MATERIALS: Different human cancer cells were injected at the lower trunk of pfp/rag2 and SCID mice to allow for local tumor growth. Data from cross sectional MRI scans were transferred to a clinical treatment planning system (TPS) for humans. Manual palpation of the tumor size was compared with calculated tumor size of the TPS and with tumor weight at necropsy. As a feasibility study MRI based treatment plans were calculated for a clinical 6MV linear accelerator using a micro multileaf collimator (µMLC). In addition, diagnostic MRI scans were used to investigate animals which did clinical poorly during the study. RESULTS: MRI is superior in precise tumor volume definition whereas manual palpation underestimates their size. Cross sectional MRI allow for treatment planning so that conformal irradiation of mice with a clinical linear accelerator using a µMLC is in principle feasible. Several internal pathologies were detected during the experiment using the dedicated scanner. CONCLUSION: MRI is a key technology for precise radiotherapy of SLA. The scanning protocols provided are suited for tumor volumetry, treatment planning, and diagnostic imaging.

Generation of 4D CT image data and analysis of lung tumour mobility during the breathing cycle.

The mobility of lung tumours during the breathing cycle is a source of error in radiotherapy treatment planning. Spatio-temporal CT data sets can be used to measure the movement of lung tumours caused by breathing. Because modern CT scanners can only scan a limited region of the body simultaneously at different times, patients have to be scanned in segments consisting of multiple slices. For studying free breathing motion multislice CT scans can be collected simultaneously with digital spirometry over several breathing cycles. The image data set is assembled by sorting the free breathing multislice CT scans according to the couch position and the tidal volume. But artefacts can occur because there are no data segments for exactly the same tidal volume and all couch positions. In this paper, a non-linear registration method is used to interpolate and reconstruct 4D CT data sets from multislice CT scans in high quality. The non-linear registration estimates a velocity field between successive scans, which is used to reconstruct a 4D CT data set by interpolating data at user-defined tidal volumes. By this technique, artefacts can be reduced significantly. Furthermore, the reconstructed 4D CT data sets are used for studying the motion of lung tumours during the respiratory cycle. The reconstructed 4D data sets of 4 patients were used to quantify the individual lung tumour motion as well as to estimate the tumour's appearance probability during a breathing cycle.

Design, performance characteristics and application examples of a new 4D motion platform.

In this publication, a three-dimensionally movable motion phantom is described and its performance characteristics are evaluated. The intended primary fields of application for the phantom are the quality assurance (QA) of respiratory motion management devices in radiation therapy (RT) like gating or tumour tracking systems, training for clinical use of these techniques, and related 4DRT research. Considering especially the QA aspect, the phantom was designed as a motion platform that can be equipped with an appropriate add-on like standard QA phantoms for dosimetric measurements. The platform is driven by three computer-controlled independent linear motors (motion range: 40 × 50 × 50 mm in anterior-posterior/superior-inferior/lateral direction; max. velocity: 3.9 m/s; max. acceleration: 10 m/s(2)), which allow the simulation of normal breathing patterns as well as arbitrary trajectories and anomalous events like coughing or baseline drift. For normal breathing patterns (here: sinusoidal curves with an amplitude of 20mm and a period of 3 s/6 s), the accuracy of the simulated motion paths was measured to be within 0,521 mm even for the ArcCHECK (weight: 20 kg) as a platform load - values that we consider to be sufficient for the intended fields of application. The respective use of the motion phantom is illustrated.

Partial body irradiation of small laboratory animals with an industrial X-ray tube.

AIMS: Dedicated precise small laboratory animal irradiation sources are needed for basic cancer research and to meet this need expensive high precision radiation devices have been developed. To avoid such expenses a cost efficient way is presented to construct a device for partial body irradiation of small laboratory animals by adding specific components to an industrial X-ray tube. METHODS AND MATERIALS: A custom made radiation field tube was added to an industrial 200 kV X-ray tube. A light field display as well as a monitor ionization chamber were implemented. The field size can rapidly be changed by individual inserts of MCP96 that are used for secondary collimation of the beam. Depth dose curves and cross sectional profiles were determined with the use of a custom made water phantom. More components like positioning lasers, a custom made treatment couch, and a commercial isoflurane anesthesia unit were added to complete the system. RESULTS: With the accessories described secondary small field sizes down to 10 by 10 mm2 (secondary collimator size) could be achieved. The dosimetry of the beam was constructed like those for conventional stereotactical clinical linear accelerators. The water phantom created showed an accuracy of 1 mm and was well suited for all measurements. With the anesthesia unit attached to the custom made treatment couch the system is ideal for the radiation treatment of small laboratory animals like mice. CONCLUSION: It was feasible to shrink the field size of an industrial X-ray tube from whole animal irradiation to precise partial body irradiation of small laboratory animals. Even smaller secondary collimator sizes than 10 by 10 mm2 are feasible with adequate secondary collimator inserts. Our custom made water phantom was well suited for the basic dosimetry of the X-ray tube.

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.

Contrast-enhanced [(18)F]fluorodeoxyglucose-positron emission tomography/computed tomography for staging and radiotherapy planning in patients with anal cancer.

PURPOSE: The practice of surgical staging and treatment of anal cancer has been replaced by noninvasive staging and combined modality therapy. For appropriate patient management, accurate lymph node staging is crucial. The present study evaluated the feasibility and diagnostic accuracy of contrast-enhanced [(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG)-positron emission tomography/computed tomography (PET/CT) for staging and radiotherapy planning of anal cancer. METHODS AND MATERIALS: A total of 22 consecutive patients (median age, 61 years old) with anal cancer underwent complete staging evaluation including physical examination, biopsy of the primary tumor, and contrast-enhanced (ce)-PET/CT. Patients were positioned as they would be for their subsequent radiotherapy. PET and CT images were evaluated independently for detectability and localization of the primary tumor, pelvic and inguinal lymph nodes, and distant metastasis. The stage, determined by CT or PET alone, and the proposed therapy planning were compared with the stage and management determined by ce-PET/CT. Data from ce-PET/CT were used for radiotherapy planning. RESULTS: ce-PET/CT revealed locoregional lymph node metastasis in 11 of 22 patients (50%). After simultaneous reading of PET and CT data sets by experienced observers, 3 patients (14%) were found to have sites of disease not seen on CT that were identified on PET. Two patients had sites of disease not seen on PET that were identified on CT. In summary, 2 patients were upstaged, and 4 patients were downstaged due to ce-PET/CT. However, radiotherapy fields were changed due to the results from ce-PET/CT in 23% of cases compared to CT or PET results alone. CONCLUSIONS: ce-PET/CT is superior to PET or CT alone for staging of anal cancer, with significant impact on therapy planning.

4D medical image computing and visualization of lung tumor mobility in spatio-temporal CT image data.

The development of 4D CT imaging has introduced the possibility of measuring breathing motion of tumors and inner organs. Conformal thoracic radiation therapy relies on a quantitative understanding of the position of lungs, lung tumors, and other organs during radiation delivery. Using 4D CT data sets, medical image computing and visualization methods were developed to visualize different aspects of lung and lung tumor mobility during the breathing cycle and to extract quantitative motion parameters. A non-linear registration method was applied to estimate the three-dimensional motion field and to compute 3D point trajectories. Specific visualization techniques were used to display the resulting motion field, the tumor's appearance probabilities during a breathing cycle as well as the volume covered by the moving tumor. Furthermore, trajectories of the tumor center-of-mass and organ specific landmarks were computed for the quantitative analysis of tumor and organ motion. The analysis of 4D data sets of seven patients showed that tumor mobility differs significantly between the patients depending on the individual breathing pattern and tumor location.