Pelvic lymph node motion during cone-beam computed tomography guided stereotactic radiotherapy.

Background and purpose: Stereotactic body radiotherapy (SBRT) is increasingly applied for pelvic lymph node recurrence. Thus far, knowledge on pelvic lymph node motion during CBCT-guided SBRT is lacking and the applied margins vary between institutions. This study evaluated pelvic lymph node motion during CBCT-guided SBRT and assessed the currently applied PTV margins of 3 and 5 mm. Material and methods: In total, 45 pelvic lymph node metastases were included. One observer delineated 45 GTVs on planning CT, 224 GTVs on pre-fraction and 216 on post-fraction CBCT. The GTV centroid coordinates were derived from all images for inter- and intrafraction motion analysis. Additionally, we assessed the influence of treatment time and lesion location on lesion motion. The expected coverage of a 3-mm and 5-mm PTV margin was assessed using the inclusiveness index for GTVs on pre- and post-fraction CBCT. Results: Lymph node interfraction motion was limited to 5 mm in 96-97 % of fractions for all translational directions and intrafraction lesion motion was limited to 3 mm in 97-100 % of fractions. Para-rectal lesions (11 %) were associated with significantly larger inter- and intrafraction motion compared to other pelvic locations and treatment duration showed no correlation with lesion motion. The mean (sd) lesion inclusiveness index was 99 % (5 %) for the 5-mm PTV margin and 96 % (9 %) for the 3-mm margin. Conclusion: Pelvic lymph node motion during CBCT-guided stereotactic radiotherapy was within the widely applied PTV margin of 5 mm, providing an opportunity to reduce this margin for pelvic lymph node SBRT.

Sexual dysfunction in women with PCOS: a case control study.

STUDY QUESTION: What is the relationship of sex steroid levels with sexual function in women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Women with PCOS reported more sexual dysfunction and more sexual distress compared to those without PCOS, but only few and weak associations between androgen levels and sexual function were observed. WHAT IS KNOWN ALREADY: The literature shows that women with PCOS report lower levels of sexual function and sexual satisfactionand more sexual distress. Contributing factors seem to be obesity, alopecia, hirsutism, acne, infertility, anxiety, depression, and low self-esteem. In women with PCOS clinical and/or biochemical hyperandrogenism is common; its relationship with sexualfunction is, however, inconclusive. STUDY DESIGN, SIZE, DURATION: This observational prospective case control study with 135 women (68 PCOS, 67 control) was conductedfrom March 2017 until March 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Heterosexual women with and without PCOS, aged 18-40 years, in a steady relationshipand without any comorbidities, underwent an extensive medical and endocrine screening using liquid chromatography-tandem mass spectrometry and validated sexual function questionnaires. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS reported significantly lower sexual function (Female Sexual Function Index (FSFI) P < 0.001, partial η2 = 0.104), higher levels of sexual distress (Female Sexual Distress Scale-Revised P < 0.001, partial η2 = 0.090), and they more often complied with the definition of sexual dysfunction (41.2% vs 11.9%, P < 0.001, Phi V = 0.331) and clinical sexual distress (51.5% vs 19.4%, P < 0.001, Phi V = 0.335). Regression analysis adjusted for confounders showed only few and weak associations between androgen levels and sexual function, with each model explaining a maximum of 15% sexual function. Following significant Group × Hormone interactions, analyses for both groups separately showed no significant associations in the PCOS group. The control group showed only weak negative associations between testosterone and FSFI pain (ß = -6.022, P = 0.044, Adj R2 = 0.050), between FAI and FSFI orgasm (ß = -3.360, P = 0.023, Adj R2 = 0.049) and between androstenedione and clinical sexual distress (ß = -7.293, P = 0.036, exp(ß) = 0.001). LIMITATIONS, REASONS FOR CAUTION: The focus of the study on sexual functioning potentially creates selection bias. Possibly women with more severe sexual disturbances did or did not choose to participate. Differences between women with PCOS and controls in relationship duration and hormonal contraceptive use might have skewed the sexual function outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Sexual function is impaired in women with PCOS. However, endocrine perturbations seem to have minimal direct impact on sexual function. Addressing sexuality and offering psychosexual counseling is important in the clinical care for women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the departments of the participating centers: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Psychosomatic OBGYN and Sexology, Leiden University Medical Center, Leiden, the Netherlands; and Department of Sexology and Psychosomatic OBGYN, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands. J.S.E.L. received unrestricted research grants from the following companies (in alphabetical order): Ansh Labs, Ferring, Merck Serono and Roche Diagnostics. He also received consultancy fees from Ansh Labs, Ferring, Titus Healthcare and Roche Diagnostics. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: CCMO register, registration number: NL55484.078.16, 10 March 2016. https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm.

Assessment of range uncertainty in lung-like tissue using a porcine lung phantom and proton radiography.

Thoracic tumours are increasingly considered indications for pencil beam scanned proton therapy (PBS-PT) treatments. Conservative robustness settings have been suggested due to potential range straggling effects caused by the lung micro-structure. Using proton radiography (PR) and a 4D porcine lung phantom, we experimentally assess range errors to be considered in robust treatment planning for thoracic indications. A human-chest-size 4D phantom hosting inflatable porcine lungs and corresponding 4D computed tomography (4DCT) were used. Five PR frames were planned to intersect the phantom at various positions. Integral depth-dose curves (IDDs) per proton spot were measured using a multi-layer ionisation chamber (MLIC). Each PR frame consisted of 81 spots with an assigned energy of 210 MeV (full width at half maximum (FWHM) 8.2 mm). Each frame was delivered five times while simultaneously acquiring the breathing signal of the 4D phantom, using an ANZAI load cell. The synchronised ANZAI and delivery log file information was used to retrospectively sort spots into their corresponding breathing phase. Based on this information, IDDs were simulated by the treatment planning system (TPS) Monte Carlo dose engine on a dose grid of 1 mm. In addition to the time-resolved TPS calculations on the 4DCT phases, IDDs were calculated on the average CT. Measured IDDs were compared with simulated ones, calculating the range error for each individual spot. In total, 2025 proton spots were individually measured and analysed. The range error of a specific spot is reported relative to its water equivalent path length (WEPL). The mean relative range error was 1.2% (1.5 SD 2.3 %) for the comparison with the time-resolved TPS calculations, and 1.0% (1.5 SD 2.2 %) when comparing to TPS calculations on the average CT. The determined mean relative range errors justify the use of 3% range uncertainty for robust treatment planning in a clinical setting for thoracic indications.

Validation of the proton range accuracy and optimization of CT calibration curves utilizing range probing.

Proton therapy is affected by range uncertainty, which is partly caused by an ambiguous conversion from x-ray attenuation to proton stopping power. CT calibration curves, or Hounsfield look-up tables (HLUTs), are institution-specific and may be a source of systematic errors in treatment planning. A range probing method to verify, optimize and validate HLUTs for proton treatment is proposed. An initial HLUT was determined according to the stoichiometric approach. For HLUT validation, three types of animal tissue phantoms were prepared: a pig's head, 'thorax' and femur. CT scans of the phantoms were taken and a structure, simulating a water slab, was added on the scan distal to the phantoms to mimic the detector used for integral depth-dose measurements. The CT scans were imported into the TPS to calculate individual pencil beams directed through the phantoms. The phantoms were positioned at the therapy system isocenter using x-ray imaging. Shoot-through pencil beams were delivered, and depth-dose profiles were measured using a multi-layer ionization chamber. Measured depth-dose curves were compared to the calculated curves and the range error per spot was determined. Based on the water equivalent path length (WEPL) of individual spot, a range error margin was defined. Ratios between measured error and theoretical margin were calculated per spot. The HLUT optimization was performed by identifying systematic shifts of the mean range error per phantom and minimizing the ratios between range errors and uncertainty margins. After optimization, the ratios of the actual range error and the uncertainty margin over the complete data set did not exceed 0.75 (1.5 SD), indicating that the actual errors are covered by the theoretical uncertainty recipe. The feasibility of using range probing to assess range errors was demonstrated. The theoretical uncertainty margins in the institution-specific setting potentially may be reduced by ~25%.

Platform for automatic patient quality assurance via Monte Carlo simulations in proton therapy.

For radiation therapy, it is crucial to ensure that the delivered dose matches the planned dose. Errors in the dose calculations done in the treatment planning system (TPS), treatment delivery errors, other software bugs or data corruption during transfer might lead to significant differences between predicted and delivered doses. As such, patient specific quality assurance (QA) of dose distributions, through experimental validation of individual fields, is necessary. These measurement based approaches, however, are performed with 2D detectors, with limited resolution and in a water phantom. Moreover, they are work intensive and often impose a bottleneck to treatment efficiency. In this work, we investigated the potential to replace measurement-based approach with a simulation-based patient specific QA using a Monte Carlo (MC) code as independent dose calculation engine in combination with treatment log files. Our developed QA platform is composed of a web interface, servers and computation scripts, and is capable to autonomously launch simulations, identify and report dosimetric inconsistencies. To validate the beam model of independent MC engine, in-water simulations of mono-energetic layers and 30 SOBP-type dose distributions were performed. Average Gamma passing ratio 99 ± 0.5% for criteria 2%/2 mm was observed. To demonstrate feasibility of the proposed approach, 10 clinical cases such as head and neck, intracranial indications and craniospinal axis, were retrospectively evaluated via the QA platform. The results obtained via QA platform were compared to QA results obtained by measurement-based approach. This comparison demonstrated consistency between the methods, while the proposed approach significantly reduced in-room time required for QA procedures.

Log file-based dose reconstruction and accumulation for 4D adaptive pencil beam scanned proton therapy in a clinical treatment planning system: Implementation and proof-of-concept.

BACKGROUND AND PURPOSE: Motion-induced uncertainties hamper the clinical implementation of pencil beam scanning proton therapy (PBS-PT). Prospective pretreatment evaluations only provide multiscenario predictions without giving a clear conclusion for the actual treatment. Therefore, in this proof-of-concept study we present a methodology for a fraction-wise retrospective four-dimensional (4D) dose reconstruction and accumulation aiming at the evaluation of treatment quality during and after treatment. MATERIAL AND METHODS: We implemented an easy-to-use, script-based 4D dose assessment of PBS-PT for patients with moving tumors in a commercially available treatment planning system. This 4D dose accumulation uses treatment delivery log files and breathing pattern records of each fraction as well as weekly repeated 4D-CT scans acquired during the treatment course. The approach was validated experimentally and was executed for an exemplary dataset of a lung cancer patient. RESULTS: The script-based 4D dose reconstruction and accumulation was implemented successfully, requiring minimal user input and a reasonable processing time (around 10 min for a fraction dose assessment). An experimental validation using a dynamic CIRS thorax phantom confirmed the precision of the 4D dose reconstruction methodology. In a proof-of-concept study, the accumulation of 33 reconstructed fraction doses showed a linear increase of D98 values. Projected treatment course D98 values revealed a CTV underdosage after fraction 25. This loss of target coverage was confirmed in a dose volume histogram comparison of the nominal, the projected (after 16 fractions) and the accumulated (after 33 fractions) dose distribution. CONCLUSIONS: The presented method allows for the assessment of the conformity between planned and delivered dose as the treatment course progresses. The implemented approach considers the influence of changing patient anatomy and variations in the breathing pattern. This facilitates treatment quality evaluation and supports decisions regarding plan adaptation. In a next step, this approach will be applied to a larger patient cohort to investigate its capability as 4D quality control and decision support tool for treatment adaptation.

Discussing reproductive health in spinal care, part II: fertility issues.

PURPOSE: Due to advancing insights, discussing fertility in spinal care is an emerging topic. Studies among neurosurgeons to evaluate clinical practice about discussing fertility are non-existent. The aim of this study is to review knowledge, attitude and practice patterns regarding discussing fertility in spinal care. METHODS: Dutch neurosurgeons and residents were sent a mail-based questionnaire addressing attitude, knowledge and practice patterns regarding discussing fertility. RESULTS: Response rate was 62 % (compared to mean of 28 % in similar surveys) with 89 questionnaires suitable for analysis. Mean age was 42 years with 83 % of respondents being male. A quarter of respondents stated neurosurgeons are responsible to discuss fertility, with 12 % indicating to actually do this. Fertility is discussed more often with patients with cauda equina syndrome (70 %) and with men (p = 0.006). Merely 8 % of respondents stated to have adequate knowledge on fertility preservation (FP); this percentage was higher for doctors with spinal surgery as specialty (p = 0.015). In case of cauda equina syndrome, doctors with more knowledge discussed fertility more often (p = 0.002). Fifty-three percent of neurosurgeons wished to enhance their knowledge, in order to feel more comfortable to discuss fertility with their patients. Five percent indicated to have ever referred a patient to a fertility specialist. CONCLUSION: With the exception of cauda equina syndrome, fertility is not routinely discussed in spinal care. Fertility is discussed more often with men. Recent guidelines state that discussing fertility is an essential part of good practice in spinal care. Education on fertility and FP needs to be integrated in the neurosurgical training program to create more awareness, and to enable clinicians to provide adequate information and care to the patient.

Proton pencil beam scanning for mediastinal lymphoma: the impact of interplay between target motion and beam scanning.

The purpose of this study was to assess the feasibility of proton pencil beam scanning (PBS) for the treatment of mediastinal lymphoma. A group of 7 patients of varying tumor size (100-800 cc) were planned using a PBS anterior field. We investigated 17 fractions of 1.8 Gy(RBE) to deliver 30.6 Gy(RBE) to the internal target volume (ITV). Spots with σ ranging from 4 mm to 8 mm were used for all patients, while larger spots (σ = 6-16 mm) were employed for patients with motion perpendicular to the beam (⩾5 mm), based on initial 4-dimensional computed tomography (4D CT) motion evaluation. We considered volumetric repainting such that the same field would be delivered twice in each fraction. The ratio of extreme inhalation amplitude and regular tidal inhalation amplitude (free-breathing variability) was quantified as an indicator of potential irregular breathing during the scanning. Four-dimensional dose was calculated on the 4D CT scans based on the respiratory trace and beam delivery sequence, implemented by partitioning the spots into separate plans on each 4D CT phase. Four starting phases (end of inhalation, end of exhalation, middle of inhalation and middle of exhalation) were sampled for each painting and 4 energy switching times (0.5 s, 1 s, 3 s and 5 s) were tested, which resulted in 896 dose distributions for the analyzed cohort. Plan robustness was measured for the target and critical structures in terms of the percent difference between 'delivered' dose (4D-evaluated) and planned dose (calculated on average CT). It was found that none of the patients exhibited highly variable or chaotic breathing patterns. For all patients, the ITV D98% was degraded by <2% (standard deviations âˆ¼ 0.1%) when averaged over the whole treatment course. For six out of seven patients, the average degradation of ITV D98% per fraction was within 5% . For one patient with motion perpendicular to the beam (⩾5 mm), the degradation of ITV D98% per fraction was up to 15%, which was mitigated to 2% by employing larger spots and repainting. Deviation of mean lung dose was at most 0.2 Gy(RBE) (less than 1% of prescribed dose, 30.6 Gy(RBE)), while the deviation of heart maximum dose and cord maximum dose could exceed 5% of the prescribed dose. No significant difference in either target coverage or normal tissue dose was observed for different energy switching times compared via two-sided Wilcoxon signed-rank tests (p < 0.05). This feasibility study demonstrates that, for mediastinal lymphoma, the impact of the interplay effect on the PBS plan robustness is minimal when volumetric repainting and/or larger spots are employed.

Performance of different three-dimensional scaffolds for in vivo endochondral bone generation.

In the context of skeletal tissue development and repair, endochondral ossification has inspired a new approach to regenerate bone tissue in vivo using a cartilage intermediate as an osteoinductive template. The aim of this study was to investigate the behavior of mesenchymal stem cells (MSCs) in regard to in vitro cartilage formation and in vivo bone regeneration when combined with different three-dimensional (3D) scaffold materials, i.e., hydroxyapatite/tricalcium phosphate (HA/TCP) composite block, polyurethane (PU) foam, poly(lactic-co-glycolic acid)/poly(ε-caprolactone) electrospun fibers (PLGA/PCL) and collagen I gel. To this end, rat MSCs were seeded on these scaffolds and chondrogenically differentiated in vitro for 4 weeks followed by in vivo subcutaneous implantation for 8 weeks. Nonetheless, the quality and maturity of in vivo ectopic bone formation appeared to be scaffold/material-dependent. Eight weeks of implantation was not sufficient to ossify the entire PLGA/PCL constructs, albeit a comprehensive remodeling of the cartilage had occurred. For HA/TCP, PU and collagen I scaffolds, more mature bone formation with rich vascularity and marrow stroma development could be observed. These data suggest that chondrogenic priming of MSCs in the presence of different scaffold materials allows the establishment of reliable templates for generating functional endochondral bone tissue in vivo without using osteoinductive growth factors. The morphology and maturity of bone formation.

The effects of titanium mesh on passive-scattering proton dose.

High-density metallic implants can introduce considerable uncertainties in proton therapy treatment planning. These uncertainties eventually translate into proton range errors, which may cause significant underdosing to the target volume or overdosing to normal tissue beyond the target. This study investigated the dosimetric impact of a 0.6 mm titanium (Ti) mesh implant in passive-scattering proton beam therapy through the study of the depth dose and output in water, and the dose profiles in solid water at various depths. The measurements were performed for a beam with a range of 8.5 cm and a modulation of 7.5 cm. The titanium mesh was placed at a depth of 1 cm below the surface of the phantom for all measurements. A range reduction of 0.5 ± 0.1 mm was observed for a beam perpendicular to the mesh, with no further reductions when the incident angle increased to 60°. We conclude that the dosimetric effect of a 0.6 mm titanium mesh implant is small for a passive scattering proton beam. With proper correction applied to metal artifacts, consistent results were observed in the phantom study in the treatment planning system.

Dosimetric consequences of pancreatic tumor motion when predetermined treatment margins are employed during intensity-modulated radiation therapy.

PURPOSE: To quantify the dosimetric consequences of pancreatic tumor motion on the pancreatic intensity-modulated radiation therapy (IMRT) plans. METHODS: Dose map of IMRT plans for 5 patients with pancreatic cancer were measured using a 2D diode array placed on a computer-controlled platform to simulate 2D pancreatic tumor motion. Dosimetric analysis was then performed to obtain IMRT quality assurance (QA) passing rates. The convolution method, which used a motion kernel to simulate 2D pancreatic motion, was also applied to the treatment and phantom verification plans for a wide range of magnitudes of motion (0.8-2.0 cm). The resulting motion-convolved verification dose maps (VDMs) were compared with the dynamic measurements to evaluate IMRT QA passing rates as well as the dose-volume histogram, the V95% of the planning target volume (PTV) and V98% of the clinical target volume (CTV). RESULTS: While CTV coverage was maintained when the simulated pancreatic tumor drifted inside the PTV with magnitudes of 1.0 cm and 1.5 cm, the V95% of the PTV was reduced by 10% and 17%, respectively. We also found that the differences between the measurements and the static VDMs increased proportional to the amplitude of motion, while the agreement between the measurements and the motion-convolved VDMs was excellent for any magnitude of motion. CONCLUSIONS: When the 4D technique is not available, predetermined margins must be used carefully to avoid possible under-dose to the target. Additionally, the phantom results show that the kernel convolution method provides an accurate evaluation of the dosimetric impact due to tumor motion and it should be employed in the planning process.

SU-E-T-602: Comparison of Treatment Techniques for Pelvic Node Irradiation: Intensity-Modulated Photons versus Protons.

PURPOSE: Radiotherapy planning for iliac pelvic nodes can be challenging due to the close proximity of sensitive healthy tissues such as the bowel and rectum. Modern treatment techniques like photon intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) offer improved healthy tissue sparing for similar target coverage. In this study we compare IMRT and IMPT plans for six post-cystectomy patients. METHODS: A dose of 50.4 Gy was prescribed to the planning target volume (PTV), which for IMRT is the clinical target volume (CTV) plus a 5 mm expansion for geometric uncertainties due to CTV and patient positioning errors, and for proton beams is the CTV plus the lateral 5 mm margin plus an additional longitudinal margin to allow for the proton range uncertainty. The optimization objectives are: 98% of the PTV receive at least 95% of the prescription, target maximum dose = 107% of prescription, rectum V[40Gy] < 30% and max = 105%, and bowel V[45Gy] < 125 cc and max = 107%. All IMRT and IMPT plans are made to achieve the target coverage objective. RESULTS: Using IMPT, the rectum would receive a mean dose of 9.0 Gy with an average (over the six patients) maximum dose of 38.1 Gy. Using IMRT, the rectum would receive a mean dose of 13.0 Gy and an average maximum dose of 37.6 Gy. The IMPT plans give a mean dose of 17.9 Gy and a maximum dose of 53.4 Gy for the bowel, whereas the IMRT plans give a mean dose of 23.8 Gy and a maximum dose of 53.2 Gy. Both the rectum and bowel show slightly lower mean doses for IMPT. CONCLUSIONS: Our results indicate that IMPT plans improve normal tissue sparing as compared to IMRT plans and provide adequate dose coverage of the target volume.

SU-E-T-437: Interfractional Dosimetric Verification of Lung Patients Treated by Passive Double Scattering Proton Radiotherapy.

PURPOSE: Proton radiotherapy, with the ability to confine the dose at desired depth, can potentially benefit lung tumor patients by significantly sparing the healthy lung tissue. However, the superior proton dose distribution could be affected by tumor shrinkage due to the quick response and by motion especially related to the respiration. Thus the treatment should be frequently verified and be adjusted accordingly if necessary to achieve the initial treatment goal. MATERIAL AND METHODS: A cohort of 20 patients were selected from lung patients treated with passive proton radiotherapy. All those patients were evaluated via 4D-CT scans and found to have tumor motion less than 1 cm. The internal target volumes (ITV) were derived based on the full inspiration and expiration phases. The average of the 4D-CT scan, full inspiration and expiration phases were used for the initial treatment planning. The planning objective was 95% of the prescription dose to at least 95% volume of the ITV. Bi-weekly verification 4D-CT scans were performed to assess the robustness of the initial treatment plan and no replanning was required for target dose variations less then 3%. RESULTS: Compared with the initial treatment plan, the standard deviations of target coverage on inspiration, expiration, and average verification CT scans are within 3% for all the patients, with the maximum difference up to 7%. No statistically significant differences were found among the initial and verification plans (p>0.1). The percentage deviations of OAR sparing were highly variable, e.g., up to 40% for mean lung dose, 100% for mean heart dose, 50% for max cord dose, particularly for OARs receiving small amount of doses. However, the absolute dose deviations are all with OAR's tolerance. CONCLUSION: Overall, the passive double scattering proton modality allows for robust proton treatment planning and delivery to treat the lung tumors with limited motion.

SU-E-J-13: A Study to Establish the Effect of CBCT Image Rotational Displacement on IGRT and ART Lung SBRT Treatments.

PURPOSE: To determine whether the accuracy of CBCT based IGRT and ART lung SBRT treatments may require extra quality assurance (QA) steps. METHODS: During CBCT Rando phantom acquisition we detected an unexpected ∼2° image rotation when comparing the CW and CCW acquired scans. Misregistered angular coordinates may Result in a rotated reconstructed image and the target localization may lead to an under- or over-dosage of the target volume (TV) and organs at risk (OARs). The effect of image rotation on CBCT-guided lung SBRT was retrospectively examined in a group of six patients treated at our institution. Patient CT sets were rotated by 1,2, and 3°. Treatment plans were recalculated using these rotated images to examine changes of dose-volume histogram indicators for IGRT and ART guided treatments. C++ simulations were run to evaluate the effect of CBCT image rotation. RESULTS: We determined through mathematical analysis that the dose coverage of the TV is dependent on its shape, location and orientation relative to isocenter. Dosimetric evaluation of lung SBRT patients showed that even for 1< Ñ2 <3°, changes in D95 to the PTV were from 2.3 ± 2.1 to 11.5 ± 3.9% for IGRT and from 8.5 ± 8.4 to 16.6 ± 8.0% for ART. Significant changes were also detected at critical structure level. CONCLUSIONS: When IGRT and ART are employed for lung SBRT treatments, significant dosimetric changes may Result from the rotation of CBCT image data sets. The extent of alterations in dose indicators depends on both the shape of the TV and its relative location to isocenter. Based on our results, angular alignment of CBCT to <1° is essential in maintaining accurate dose delivery of IGRT and ART based lung SBRT treatments.

SU-E-J-153: Volumetric and Dosimetric Variations of Post-Prostatectomy Patients Treated with Radiation Therapy and Endorectal Ballon.

PURPOSE: Post-prostatectomy patients may be treated with endorectal balloon (ERB) placed during the radiation therapy. The objectives of this tudy are to investigate geometrical variation of organs at risk (OAR) and CTVs (based on RTOG and EORTC guidelines) throughout the course of radiation therapy and their dosimetric impact. METHODS: Six consecutive post-prostatectomy patients enrolled on a prospective IRB approved institutional study were analyzed. Patients underwent CT/MRI simulation and treatment with daily endorectal balloon (ERB). Six T2-MRI scans were performed during the treatment course. Bladder, rectum and two sets of CTVs according to the RTOG and EORTC guidelines were contoured by physician on each of the weekly MRI scans. The MRI scans were subsequently rigidly fused to the CT simulation images to simulate daily kV-kV patient alignment. RESULTS: 1. A consistent trend of decreasing bladder volume was found after the first week of treatment and therefore the V65Gy was found to increase after the second week of the treatment.2. The rectal volume with ERB was found to be relatively consistent during the treatment course. Displacements of rectal contours were within 2mm in all directions. The V60Gy<20% (our institutional rectal constraint) varied on average less than 2%.3. We found that the CTV volumes contoured per EORTC guideline exhibits a larger variation than those drawn according to the RTOG guidelines most likely due to the bladder exclusion imposed by it. While the average variation of RTOG based CTV volume was found within 5%, the variation of CTV-EROTC volumes was more then 10%) (p = 0.06). CONCLUSIONS: In post-prostatectomy patients undergoing radiotherapy with daily ERB had a consistent decrease in the bladder volume during the treatment leading to increased bladder irradiation and changes in the CTV volumes predominantly when EORTC guideline were followed.

Toxicity data for preoperative concurrent chemoradiotherapy with oxaliplatin and continuous infusion 5-fluorouracil for locally advanced esophageal cancer.

The purpose of this retrospective analysis was to characterize the feasibility and tolerability of oxaliplatin/5-fluorouracil (5-FU) given concurrently with radiotherapy for patients with locally advanced esophageal cancer. Between July 2005 and March 2009, 15 patients with clinical stage T3/T4 and/or N1/M1a lower esophageal or gastroesophageal junction adenocarcinoma were treated with preoperative chemoradiotherapy using oxaliplatin every 2 weeks and continuous infusion 5-FU. The main treatment-related toxicities were oral mucositis and dysphagia. During the first 2 weeks of treatment, 20% of patients presented with grade 1-2 oral mucositis, and one patient developed grade 1 dysphagia. In weeks 3-4, 53% of the patients experienced grade 1-2 mucositis, and 40% experienced grade 1-2 dysphagia. One patient only experienced grade 3 mucositis in week 4. Three patients (20%) had grade 3-4 dysphagia in weeks 3-4 and were continued on intravenous fluids and pain medications. During the last 2 weeks of chemoradiotherapy, 53% of patients reported grade 1-2 oral mucositis, mostly grade 1 and 73% of patients experienced grade 1-2 dysphagia and 26% patients experienced grade 3-4 dysphagia. Other toxicities included fatigue, nausea, neuropathy, and diarrhea. Only one patient experienced > 10% weight loss. The whole group was treated with aggressive supportive care during radiotherapy. Five (33%) patients achieved a pathological complete response. No patients developed locoregional failure. Sixty percent of the patients developed distant metastases and the 2-year disease-free survival was 53%. The median survival was 3.2 years with the 2-year overall survival of 73%. Preoperative oxaliplatin/5-FU-based chemoradiotherapy for locally advanced esophageal cancer is feasible, but associated with substantial gastrointestinal toxicity. A careful attention to nutrition and hydration throughout the course of therapy is required.

Relation between in vitro and in vivo osteogenic potential of cultured human bone marrow stromal cells.

The use of cell therapies in bone reconstruction has been the subject of extensive research. It is known that human bone marrow stromal cell (HBMSC) cultures contain a population of progenitor cells capable of differentiation towards the osteogenic lineage. In the present study, the correlation between the in vitro osteogenic potential of HBMSC cultures and their capacity to form bone in vivo was investigated. HBMSC cultures were established from 14 different donors. Fourth passage cells were examined for the expression of alkaline phosphatase (ALP), procollagen I (PCI) and osteopontin (OP), through flow cytometry and the effect of the osteogenic differentiation factor dexamethasone (Dex) on this expression was evaluated. In addition, the capacity of the cultures to induce in vivo bone formation was analysed by culturing the cells on porous hydroxyapatite (HA) scaffolds followed by subcutaneous implantation of these constructs in nude mice. Results showed expression of PCI, OP and ALP in all cultures, irrespective of the presence of Dex in the culture medium. Dex failed to have a significant effect on the expression of PCI and OP but it induced a consistent increase in the relative amount of cells expressing ALP. Nevertheless, although in vitro testing clearly indicated osteogenic potential in all cultures, HBMSC from six of the 14 tested donors did not form bone in vivo. The results, therefore, demonstrate that neither the expression of PCI, OP and ALP nor the absolute increase in Dex-stimulated ALP expression can as yet be used as predictive markers for in vivo bone formation by HBMSC. However, preliminary data indicate that not the absolute, but the relative increase in the percentage of ALP expressing cells caused by Dex stimulation may be related to the ability of the HBMSC to form bone.

Bone tissue-engineered implants using human bone marrow stromal cells: effect of culture conditions and donor age.

At present, it is well known that populations of human bone marrow stromal cells (HBMSCs) can differentiate into osteoblasts and produce bone. However, the amount of cells with osteogenic potential that is ultimately obtained will still be dependent on both patient physiological status and culture system. In addition, to use a cell therapy approach in orthopedics, large cell numbers will be required and, as a result, knowledge of the factors affecting the growth kinetics of these cells is needed. In the present study we investigated the effect of dexamethasone stimulation on the in vivo osteogenic potential of HBMSCs. After a proliferation step, the cells were seeded and cultured on porous calcium phosphate scaffolds for 1 week, and then subcutaneously implanted in nude mice for 6 weeks, in order to evaluate their in vivo bone-forming ability. Furthermore, the effect of donor age on the proliferation rate of the cultures and their ability to induce in vivo bone formation was studied. In 67% of the assayed patients (8 of 12), the presence of dexamethasone in culture was not required to obtain in vivo bone tissue formation. However, in cultures without bone-forming ability or with a low degree of osteogenesis, dexamethasone increased the bone-forming capacity of the cells. During cellular proliferation, a significant age-related decrease was observed in the growth rate of cells from donors older than 50 years as compared with younger donors. With regard to the effect of donor age on in vivo bone formation, HBMSCs from several donors in all age groups proved to possess in vivo osteogenic potential, indicating that the use of cell therapy in the repair of bone defects can be applicable irrespective of patient age. However, the increase in donor age significantly decreased the frequency of cases in which bone formation was observed.

[Drug therapy of carcinoids of the gastrointestinal tract]. / Medikamentöse Therapie bei Karzinoiden des Gastrointestinaltraktes.

Carcinoid tumors are rare and slowly growing neuroendocrine tumors of the foregut, midgut and hindgut. Drug therapy is of special importance in patients with inoperable metastasising disease. This palliative therapy is aimed at reduction of the hormone-dependent symptoms and inhibition of tumor growth. Somatostatin analogues, alpha-interferon and various chemotherapeutic agents are used for this purpose. Drug therapy can be supplemented by surgical and radiological intervention through interdisciplinary cooperation of the surgeon, radiologist, endocrinologist and gastroenterologist.