A dedicated cloud system for real-time upfront quality assurance in pediatric radiation therapy.

PURPOSE: Pediatric radiotherapy (RT) is a highly specialized field, requiring great experience to delineate correctly tumor targets and organs at risk. To reduce treatment failures related to planning inaccuracies and to obtain robust clinical results despite the limited numbers of enrolled pediatric patients, the SIOP PNET5MB clinical trial on medulloblastoma requires a real-time, pre-radiation review of the RT treatment (craniospinal irradiation and boost plan) under the direct responsibility of the national coordinator center. Here we describe the centralized radiotherapy quality assurance (QA) program developed in Italy for this purpose. METHODS: Using the software package VODCA (MSS, Hagendorn, Switzerland, www.vodca.ch ), we developed a cloud platform able to handle computed tomography (CT) images and RT objects and to support the complete workflow required by the review process in the context of the SIOP PNET5 trial. RESULTS: All Italian centers participating in the PNET5 trial adopted the proposed QA system. 24 patients were successfully enrolled and reviewed. For 15 patients (62.5%), one or more plan revisions were requested for the craniospinal irradiation plan and for 11 patients (45.8%) plan revisions were requested for the boost. RT was delivered after the plan was centrally approved for all enrolled patients. So far, in Italy, no patients have been excluded from PNET5 due to dosimetric incompliance to the protocol or for exceeding the RT starting time limit. CONCLUSION: The cloud platform successfully supported the trial workflow, producing official review documents. This efficient QA was crucial to guarantee optimized treatments and protocol compliance for all pediatric patients enrolled in the SIOP protocol.

Characterisation of rectal motion during neo-adjuvant radiochemotherapy for rectal cancer with image-guided tomotherapy: implications for adaptive dose escalation strategies.

BACKGROUND: Interest in boosting the dose to the tumour during neo-adjuvant radiochemotherapy for rectal cancer is ever increasing, especially within the frame of adaptive radiotherapy. Rectal motion remains a potentially important obstacle to the full exploitation of this approach and needs to be carefully investigated. MATERIAL AND METHODS: The main purposes of this work were to: a) quantify rectal motion on all fractions of a treatment course; and b) assess margins for adaptive boosting in the second part of the treatment in order to benefit of tumour reduction during treatment. Ten consecutive patients treated with image-guided tomotherapy (41.4 Gy, 18 fractions) were selected. The cranial half of the rectum (subject to motion) was contoured by a single observer on daily MVCTs. The variations of rectal volume and of the envelope of rectum positions were investigated (169 MVCTs). The impact of applying different margins to the rectum in including all its possible positions was also investigated when considering the planning kVCT, the first fraction MVCT, the half-treatment MVCT or the median rectal contours of the whole or second half of treatment as reference volumes. RESULTS: Rectal volume reduced during treatment in all patients, with a significant time-trend in 6/10 patients. The median values of the envelope volumes were 129 cm(3) and 87 cm(3) in the first and second half of the treatment, respectively. On average, 95% of the rectal envelope was included by an isotropic expansion of 12 mm and 5 mm of the median contours when considering the whole or the second half of the treatment, respectively. CONCLUSION: A significant reduction of rectal volume was found in the second part of the treatment where rectal mobility was limited. As a consequence, relatively small margins may be used around the residual tumour volume when adaptive boost is delivered in the second half of the treatment.

Systematic literature review on the benefit of patient protection shielding during medical X-ray imaging: Towards a discontinuation of the current practice.

PURPOSE: Patient shielding during medical X-ray imaging has been increasingly criticized in the last years due to growing evidence that it often provides minimal benefit and may even compromise image quality. In Europe, and as also shown in a short assessment in Switzerland, the use of patient shielding is inhomogeneous. The aim of this study was to systematically review recent literature in order to assess benefits and appraise disadvantages related to the routine use of patient shielding. METHODS: To evaluate benefits and disadvantages related to the application of patient shielding in radiological procedures, a systematic literature review was performed for CT, radiography, mammography and fluoroscopy-guided medical X-ray imaging. In addition, reports from medical physics societies and authorities of different countries were considered in the evaluation. RESULTS: The literature review revealed 479 papers and reports on the topic, from which 87 qualified for closer analysis. The review considered in- and out-of-plane patient shielding as well as shielding for pregnant and pediatric patients. Dose savings and other dose and non-dose related effects of patient shielding were considered in the evaluation. CONCLUSIONS: Although patient shielding has been used in radiological practice for many years, its use is no longer undisputed. The evaluation of the systematic literature review of recent studies and reports shows that dose savings are rather minimal while significant dose- and non-dose-related detrimental effects are present. Consequently, the routine usage of patient protection shielding in medical X-ray imaging can be safely discontinued for all modalities and patient groups.

ESTRO ACROP: Technology for precision small animal radiotherapy research: Optimal use and challenges.

Many radiotherapy research centers have recently installed novel research platforms enabling the investigation of the radiation response of tumors and normal tissues in small animal models, possibly in combination with other treatment modalities. Many more research institutes are expected to follow in the coming years. These novel platforms are capable of mimicking human radiotherapy more closely than older technology. To facilitate the optimal use of these novel integrated precision irradiators and various small animal imaging devices, and to maximize the impact of the associated research, the ESTRO committee on coordinating guidelines ACROP (Advisory Committee in Radiation Oncology Practice) has commissioned a report to review the state of the art of the technology used in this new field of research, and to issue recommendations. This report discusses the combination of precision irradiation systems, small animal imaging (CT, MRI, PET, SPECT, bioluminescence) systems, image registration, treatment planning, and data processing. It also provides guidelines for reporting on studies.

Introducing gel dosimetry in a clinical environment: customization of polymer gel composition and magnetic resonance imaging parameters used for 3D dose verifications in radiosurgery and intensity modulated radiotherapy.

Radiation sensitive gels have been used as dosimeters for clinical dose verification of different radiation therapy modalities. However, the use of gels is not widespread, because careful techniques are required to achieve the dose precision and accuracy aimed for in clinical dose verification. Here, the introduction of gel dosimetry in a clinical environment is described, including the whole chain of customizations and preparations required to introduce magnetic resonance (MR) based gel dosimetry into clinical routine. In order to standardize gel dosimetry in dose verifications for radiosurgery and intensity modulated radiotherapy (IMRT), we focused on both the customization of the gel composition and of the MR imaging parameters to increase its precision. The relative amount of the components of the normoxic, methacrylic acid based gel (MAGIC) was changed to obtain linear and steep dose response relationships. MR imaging parameters were customized for the different dose ranges used in order to lower the relative standard deviation of the measured transversal relaxation rate (R2). An optimization parameter was introduced to quantify the change in the relative standard deviation of R2 (sigma(R2,rel)) taking the increase in MR time into account. A 9% methacrylic acid gel customized for radiosurgery was found to give a linear dose response up to 40 Gy with a slope of 0.94 Gy(-1) s(-1), while a 6% methacrylic acid gel customized for IMRT had a linear range up to 3 Gy with a slope of 1.86 Gy(-1) s(-1). With the help of an introduced optimization parameter, the mean sigma(R2,rel) was improved by 13% for high doses and by 55% for low doses, without increasing MR time to unacceptable values. A mean dose resolution of less than 0.13 Gy has been achieved with the gel and imaging parameters customized for IMRT and a dose resolution from 0.97 Gy (at 5 Gy) to 2.15 Gy (at 40 Gy) for the radiosurgery dose range. The comparisons of calculated and measured relative 3D dose distributions performed for radiosurgery and IMRT showed an acceptable overall correlation. The gamma criterion for the radiosurgery verification with a voxel size of 1.5 x 1.5 x 1.5 mm3 was passed by 96.8% of the voxels (1.5 mm distance, 8% in dose). For the IMRT verification using a voxel size of 1.25 x 1.25 x 5 mm3 the gamma criterion was passed by 50.3% of the voxels (3 mm distance, 3% dose uncertainty). Using dedicated data analysis and visualization software, MR based normoxic gel dosimetry was found to be a valuable tool for clinically based dose verification, provided that customized gel compositions and MR imaging parameters are used. While high dose precision was achieved, further work is required to achieve clinically acceptable dose accuracy.

Evaluating the relationship between erectile dysfunction and dose received by the penile bulb: using data from a randomised controlled trial of conformal radiotherapy in prostate cancer (MRC RT01, ISRCTN47772397).

AIM: To evaluate the relationship between erectile function and the radiation dose to the penile bulb and other proximal penile structures in men receiving conformal radiotherapy (CFRT) for prostate cancer (PCa). METHODS: The Medical Research Council (MRC) RT01 trial randomised 843 men who had localised PCa to receive either 64 or 74 Gy after 3 - 6 months neoadjuvant hormonal treatment. Fifty-one men were selected who were potent prior to hormonal treatment, having completed both pre-hormone and 2-year post-CFRT Quality of Life assessments, and on whom dose volume data were available for analysis. The men were divided into three groups according to 2-year follow-up: potent, reduced potency, and impotent. The bulb of the penis together with the crura, were outlined on restored treatment plans. Dose - volume histograms were generated and compared between the three groups. An ordered logistic regression model was used to calculate the odds ratio of a range of dose - volume parameters to the penile bulb and effect on erectile dysfunction. The dose to the penile bulb was correlated to the dose received by the crura. RESULTS: Of the 51 patients, 12 remained potent, 22 had reduced potency, and 17 were impotent at 2 years. No differences were seen in mean dose to the penile bulb by allocated treatment (t test = 1.61, p = 0.11). The mean doses to the penile bulb received by the potent, reduced potency, and impotent groups were 45.5 Gy (SD 17.1), 48 Gy (SD 16.1), and 59.2 Gy (SD 13.8), respectively. There was a strong correlation between the mean dose received by the penile bulb and dose to the crura (r = 0.82, p < 0.0001). 83.3% of impotent patients received a D90 > or = 50 Gy to the penile bulb compared with 29.4% of patients who maintained potency at 2 years (p = 0.006). CONCLUSION: There is evidence from this study to suggest a dose volume effect on the penile bulb and erectile dysfunction. A D90 > or = 50 Gy is associated with a significant risk of erectile dysfunction and this should form a basis for selecting dose constraints in future dose escalation studies.

[Application of normoxic polymer gels in 3D-dosimetry for radiosurgery]. / Einsatz normoxischer Polymergele in der 3D-Dosimetrie für die Radiochirurgie.

The aim of this study was to describe the manufacture of normoxic polymer gels, to characterize their dose response relationship, to optimize MR imaging parameters in order to minimize the standard deviation in the measured dose and to use the gel in a dose verification experiment in radiosurgery. The normoxic polymer gel used is simple to manufacture under normal atmospheric conditions and is characterized by a linear dose relationship up to 40 Gy. MR imaging was performed using 2-dimensional (20) single spin echo pulse sequences with two different echo times. The imaging parameters were optimized in order to minimize the standard deviation of the measured transversal relaxation rate R2 and to achieve a geometrical resolution of 1.5 mm. Comparisons of calculated and measured relative 3D dose distributions using a multi isocentric irradiation with Gamma Knife B showed a good overall agreement of both the isodose levels and the differential and cumulative dose volume histograms. The standard deviation in the measured dose was approximately 9% at 30 Gy. The evaluation according to the gamma criterion showed that 96% of the dose voxels remained within a spatial uncertainty of 1.5 mm and a dose uncertainty of 8%.

First application of a pixel-wise analysis on bladder dose-surface maps in prostate cancer radiotherapy.

PURPOSE: To develop a method for investigating local dose effects on the bladder after prostate cancer radiotherapy based on dose-surface maps (DSMs). BACKGROUND AND PURPOSE: DSMs of patients included in a prospective study (DUE01) were generated by virtually cutting bladder contours at the points intersecting the sagittal plane passing through its center-of-mass: maps were laterally normalized and aligned at the posterior inferior point. The average DSMs of patients with/without toxicity, the DSMs of differences and t statistic were used to select regions better discriminating patients with toxicity. A total of 72 patients with no/mild urinary symptoms before radiotherapy and who were treated with moderate hypo-fractionation (2.5-2.65Gy/fr, 70-74Gy) were considered, and the endpoint was an International Prostate Symptoms Score (IPSS)⩾15 at the end of therapy (IPSSend⩾15, n=25/72). RESULTS: The DSMs of patients with/without toxicity were significantly different (p<0.05). The percentage of bladder circumference receiving >50-70Gy at 5-7mm from the base was associated with an IPSSend⩾15 (odds ratios: 1.03-1.07). Different patterns were recognized for specific symptoms. With frequency/urgency, a quasi-threshold effect on the absolute posterior dose at 5-12mm from the base (2Gy equivalent doses=80-82Gy, α/ß=3-5Gy) was observed. CONCLUSIONS: Local-dose effects for acute symptoms were detected in a group of patients treated within a moderately hypo-fractionated protocol. The results for frequency/urgency were consistent with a threshold effect on the trigone.

Precision dosimetry for narrow photon beams used in radiosurgery-determination of Gamma Knife output factors.

Treatment units for radiosurgery, like Leksell Gamma Knife and adapted, or dedicated, linear accelerators use small circular beams of ionizing radiation down to 4 mm in diameter at the isocenter. By cross-firing, these beams generate a high dose region at the isocenter together with steep dose gradients of up to 30% per mm. These units are used to treat small complex shaped lesions, often located close to critical structures within the brain, by superimposing several single high dose regions. In order to commission such treatment units for stereotactic irradiations, to carry out quality assurance and to simulate treatment conditions, as well as to collect input data for treatment planning, a precise dosimetric system is necessary. Commercially available radiation dosimeters only partially meet the requirements for narrow photon beams and small field sizes as used in stereotactic treatment modalities. The aim of this study was the experimental determination of the output factors for the field defining collimators used in Gamma Knife radiosurgery, in particular for the smallest, the 4 mm collimator helmet. For output factor measurements a pin point air ionization chamber, a liquid ionization chamber, a diode detector, a diamond detector, TLD microcubes and microrods, alanine pellets, and radiochromic films were used. In total, more than 1000 measurements were performed with these different detection systems, at the sites in Munich and Zurich. Our results show a resultant output factor for the 4 mm collimator helmet of 0.8741 +/- 0.0202, which is in good agreement with recently published results and demonstrates the feasibility of such measurements. The measured output factors for the 8 mm and 14 mm collimator helmets are 0.9578 +/- 0.0057 and 0.9870 +/- 0.0086, respectively.

Three-dimensional dose verification using BANG gel: a clinical example.

OBJECT: The authors sought to demonstrate the possible value of three-dimensional dose verification by using gel dosimetry. METHODS: In this study, commercially available BANG-25 Gy gel was used. This polymer gel is tissue equivalent and the relaxation rate (R2) measured using magnetic resonance (MR) imaging is proportional to the absorbed dose in the gel. A cylindrical container filled with BANG was mounted within an anthropomorphic head phantom and was handled using the same process as would be used for a patient undergoing gamma knife radiosurgery (GKS). An irregular target outline was constructed and a dose plan was created consisting of seven shots, three using the 8-mm and four using the 4-mm collimator helmet. The maximum dose specified was 25 Gy. A combination of several single spin-echo MR imaging sequences with different echo times was used to calculate the R2. The geometric resolution of the MR images was approximately 1 mm3. To compare the measured dose distribution with the calculated one, isodoses were overlaid in three orthogonal planes by using specially designed analysis software. CONCLUSIONS: Comparisons of the measured and calculated relative dose distributions showed good overall agreement, with differences of less than 3 mm between measured and calculated isodoses. High resolution BANG gel dosimetry for GKS can be useful for the verification of clinical treatment plans, especially when multiple shots are involved. Further verifications will be done using additional imaging parameters and absolute dose calibrations to improve the method.

A cylindrical model of the rectum: comparing dose-volume, dose-surface and dose-wall histograms in the radiotherapy of prostate cancer.

The calculation of the percentage cumulative histogram of the rectal wall (DWH) in prostate cancer radiotherapy may be subject to large uncertainties due to the difficulty of assessing the wall thickness on CT images. For this reason often only the external contour is used to define the rectum and then the percentage cumulative dose-volume histogram (DVH) of the rectum including any filling is calculated as a 'surrogate' for the DWH. More recently, other approaches using only the external contour have been proposed to estimate the DWH such as the percentage normalized dose-surface histograms (NDSH). A similar concept can be used when considering the solid rectum (the percentage normalized DVH, NDVH). The purpose of this investigation was to assess the relationships between rectal DVH, NDVH, DSH, NDSH and DWH in the common case of three- and four-field techniques in prostate cancer irradiation. Analytical relationships between the above parameters have been derived for a cylindrical rectum model in the case of three- and four-field techniques. The model is applied to the case of an empty rectum, a full rectum and to the more realistic mixed full/empty rectum situation for a four-field technique delivering 76 Gy (ICRU dose) with 18 MV x-rays. Different positions of the lateral beam with respect to the rectum axis were simulated. In the case of no lumen variation along the z-axis, the DWH is found to be very close to the DVH and to the DSH for empty and full rectum, respectively. The largest differences (up to 15%) between DVH and DSH were seen in the high-dose region (>70 Gy). In the more realistic case of lumen variation along the z-axis, the DWH always lies between NDVH and NDSH and, excluding the full-rectum situation, the DWH differs from the DVH by less than 7% in the 50-75 Gy range. In the case of significant portions of rectum being completely shielded, the DVH may differ from the NDVH/NDSH/DWH by up to 10-15%. In most clinical situations NDVH is within a few per cent of DWH, whilst NDSH may differ from DWH by up to 15-20%, especially in the high-dose region (V70). In conclusion, for most situations, the DVH is highly correlated with NDVH and DWH. A high degree of consistency between NDVH and DWH was found in most clinical cases whilst largest deviations between NDSH and DWH were evident in the high-dose region (70-75 Gy). In the less common case of a very full rectum a poorer correlation between DVH/NDVH and DWH was found whilst NDSH mimicked the DWH very well. In summary, except for the case of a 'very full' rectum, NDVH may be used as a robust surrogate for DWH. The DVH seems to be sufficiently robust if the rectum is prevalently empty.

Correlation between surrogates of bladder dosimetry and dose-volume histograms of the bladder wall defined on MRI in prostate cancer radiotherapy.

The correlation between bladder dose-wall-histogram (DWH) and dose-volume-histogram (DVH), dose-surface-histogram (DSH), and DVH-5/10 was investigated in a group of 28 patients; bladder walls were drawn on T2-MRI. DVH showed the poorest correlation with DWH; DSH or DVH-5/10 should be preferred in planning; absolute DVH may be used for radical patients, although less robust.

Systematic evaluation of three different commercial software solutions for automatic segmentation for adaptive therapy in head-and-neck, prostate and pleural cancer.

PURPOSE: To validate, in the context of adaptive radiotherapy, three commercial software solutions for atlas-based segmentation. METHODS AND MATERIALS: Fifteen patients, five for each group, with cancer of the Head&Neck, pleura, and prostate were enrolled in the study. In addition to the treatment planning CT (pCT) images, one replanning CT (rCT) image set was acquired for each patient during the RT course. Three experienced physicians outlined on the pCT and rCT all the volumes of interest (VOIs). We used three software solutions (VelocityAI 2.6.2 (V), MIM 5.1.1 (M) by MIMVista and ABAS 2.0 (A) by CMS-Elekta) to generate the automatic contouring on the repeated CT. All the VOIs obtained with automatic contouring (AC) were successively corrected manually. We recorded the time needed for: 1) ex novo ROIs definition on rCT; 2) generation of AC by the three software solutions; 3) manual correction of AC.To compare the quality of the volumes obtained automatically by the software and manually corrected with those drawn from scratch on rCT, we used the following indexes: overlap coefficient (DICE), sensitivity, inclusiveness index, difference in volume, and displacement differences on three axes (x, y, z) from the isocenter. RESULTS: The time saved by the three software solutions for all the sites, compared to the manual contouring from scratch, is statistically significant and similar for all the three software solutions. The time saved for each site are as follows: about an hour for Head&Neck, about 40 minutes for prostate, and about 20 minutes for mesothelioma. The best DICE similarity coefficient index was obtained with the manual correction for: A (contours for prostate), A and M (contours for H&N), and M (contours for mesothelioma). CONCLUSIONS: From a clinical point of view, the automated contouring workflow was shown to be significantly shorter than the manual contouring process, even though manual correction of the VOIs is always needed.

Contouring variability of the penile bulb on CT images: quantitative assessment using a generalized concordance index.

PURPOSE: Within a multicenter study (DUE-01) focused on the search of predictors of erectile dysfunction and urinary toxicity after radiotherapy for prostate cancer, a dummy run exercise on penile bulb (PB) contouring on computed tomography (CT) images was carried out. The aim of this study was to quantitatively assess interobserver contouring variability by the application of the generalized DICE index. METHODS AND MATERIALS: Fifteen physicians from different Institutes drew the PB on CT images of 10 patients. The spread of DICE values was used to objectively select those observers who significantly disagreed with the others. The analyses were performed with a dedicated module in the VODCA software package. RESULTS: DICE values were found to significantly change among observers and patients. The mean DICE value was 0.67, ranging between 0.43 and 0.80. The statistics of DICE coefficients identified 4 of 15 observers who systematically showed a value below the average (p value range, 0.013 - 0.059): Mean DICE values were 0.62 for the 4 "bad" observers compared to 0.69 of the 11 "good" observers. For all bad observers, the main cause of the disagreement was identified. Average DICE values were significantly worse from the average in 2 of 10 patients (0.60 vs. 0.70, p < 0.05) because of the limited visibility of the PB. Excluding the bad observers and the "bad" patients," the mean DICE value increased from 0.67 to 0.70; interobserver variability, expressed in terms of standard deviation of DICE spread, was also reduced. CONCLUSIONS: The obtained values of DICE around 0.7 shows an acceptable agreement, considered the small dimension of the PB. Additional strategies to improve this agreement are under consideration and include an additional tutorial of the so-called bad observers with a recontouring procedure, or the recontouring by a single observer of the PB for all patients included in the DUE-01 study.

Dose-volume constraints to reduce rectal side effects from prostate radiotherapy: evidence from MRC RT01 Trial ISRCTN 47772397.

PURPOSE: Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>/=50 Gy). Evidence is emerging that lower doses could also be important. METHODS AND MATERIALS: Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. RESULTS: A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30