A comparative analysis between radiation dose intensification and conventional fractionation in neoadjuvant locally advanced rectal cancer: a monocentric prospective observational study.

PURPOSE: The potential role of neoadjuvant radiation dose intensification in locally advanced rectal cancer (LARC) is still largely debated. In the present study, a comparative analysis between radiation dose intensification and conventional fractionation was performed. MATERIALS AND METHODS: In the current prospective observational study (protocol ID RT-03/2011), 56 patients diagnosed with LARC were enrolled between January 2013 and December 2016. More specifically, 25 patients underwent preoperative conventional radiation dose [i.e., 50.4 Gy in 28 fractions here defined as standard dose radiotherapy (SDR)-group 1], whereas 31 patients were candidate for radiation dose intensification (RDI) (i.e., 60 Gy in 30 fractions-group 2). The primary endpoint was the complete pathological response (pCR) rate. Secondary endpoints were postoperative complications and ChT-RT-related toxicity. RESULTS: No statistical significance was observed in pCR rate (20.8% and 22.6% in SDR and RDI group, respectively, p = 0.342). Of contrast, the RDI group showed a significantly higher primary tumor downstaging in case of T3 tumor compared to SDR group (p = 0.049). Sphincter-preserving surgery was 84% and 93.5% in SDR and RDI groups, respectively (p = 0.25). All patients had R0 margins. No surgical-related death was recorded. No statistically significant difference was observed regarding surgical complications and incomplete mesorectal excision. Acute genitourinary toxicity was significantly higher in RDI group (p = 0.015). CONCLUSIONS: The intensification of the neoadjuvant radiotherapy for LARC seems to produce a major pathological response in T3 tumors. The radiation dose intensification appears probably associated with a higher rate of genitourinary toxicity.

Small bowel protection in IMRT for rectal cancer : A dosimetric study on supine vs. prone position.

BACKGROUND: This treatment planning study analyzes dose coverage and dose to organs at risk (OAR) in intensity-modulated radiotherapy (IMRT) of rectal cancer and compares prone vs. supine positioning as well as the effect of dose optimization for the small bowel (SB) by additional dose constraints in the inverse planning process. PATIENTS AND METHODS: Based on the CT datasets of ten male patients in both prone and supine position, a total of four different IMRT plans were created for each patient. OAR were defined as the SB, bladder, and femoral heads. In half of the plans, two additional SB cost functions were used in the inverse planning process. RESULTS: There was a statistically significant dose reduction for the SB in prone position of up to 41% in the high and intermediate dose region, compared with the supine position. Furthermore, the femoral heads showed a significant dose reduction in prone position in the low dose region. Regarding the additional active SB constraints, the dose in the high dose region of the SB was significantly reduced by up to 14% with the additional cost functions. There were no significant differences in the dose distribution of the planning target volume (PTV) and the bladder. CONCLUSION: Prone positioning can significantly reduce dose to the SB in IMRT for rectal cancer and therefore should not only be used in 3D conformal radiotherapy but also in IMRT of rectal cancer. Further protection of the SB can be achieved by additional dose constraints in inverse planning without jeopardizing the homogeneity of the PTV.

Anterior-oriented proton beams for prostate cancer: A multi-institutional experience.

BACKGROUND: Proton beam therapy (PBT) for prostate cancer generally involves the use of two lateral beams that transverse the hips. In patients with hip replacements or a previously irradiated hip, this arrangement is contraindicated. The use of non-lateral beams is possible, but not well described. Here we report a multi-institutional experience for patients treated with at least one non-lateral proton beam for prostate cancer. MATERIAL AND METHODS: Between 2010 and 2014, 20 patients with organ-confined prostate cancer and a history of hip prosthesis underwent proton therapy utilizing at least one anterior oblique beam (defined as between 10° and 85° from vertical) at one of three proton centers. RESULTS: The median follow-up was 6.4 months. No patients have developed PSA failure or distant metastases. The median planning target volume (PTV) D95 was 79.2 Gy (RBE) (range 69.7-79.9). The median rectal V70 was 9.2% (2.5-15.4). The median bladder V50, V80, and mean dose were 12.4% (3.7-27.1), 3.5 cm3 (0-7.1), and 14.9 Gy (RBE) (4.6-37.8), respectively. The median contralateral femur head V45 and max dose were 0.01 cm3 (0-16.6) and 43.7 Gy (RBE) (15.6-52.5), respectively. The incidence of acute Grade 2 urinary toxicity was 40%. There were no Grade≥3 urinary toxicities. There was one patient who developed late Grade 2 rectal proctitis, with no other cases of acute or late ≥Grade 2 gastrointestinal toxicity. Grade 2 erectile dysfunction occurred in two patients (11.1%). Mild hip pain was experienced by five patients (25%). There were no cases of hip fracture. CONCLUSION: PBT for prostate cancer utilizing anterior oblique beam trajectories is feasible with favorable dosimetry and acceptable toxicity. Further follow-up is needed to assess for long-term outcomes and toxicities.

Evaluation of electric field distribution in electromagnetic stimulation of human femoral head.

Electromagnetic stimulation is a common therapy used to support bone healing in the case of avascular necrosis of the femoral head. In the present study, we investigated a bipolar induction screw system with an integrated coil. The aim was to analyse the influence of the screw parameters on the electric field distribution in the human femoral head. In addition, three kinds of design parameters (the shape of the screw tip, position of the screw in the femoral head, and size of the screw insulation) were varied. The electric field distribution in the bone was calculated using the finite element software Comsol Multiphysics. Moreover, a validation experiment was set up for an identical bone specimen with an implanted screw. The electric potential of points inside and on the surface of the bone were measured and compared to numerical data. The electric field distribution within the bone was clearly changed by the different implant parameters. Repositioning the screw by a maximum of 10 mm and changing the insulation length by a maximum of 4 mm resulted in electric field volume changes of 16% and 7%, respectively. By comparing the results of numerical simulation with the data of the validation experiment, on average, the electric potential difference of 19% and 24% occurred when the measuring points were at a depth of approximately 5 mm within the femoral bone and directly on the surface of the femoral bone, respectively. The results of the numerical simulations underline that the electro-stimulation treatment of bone in clinical applications can be influenced by the implant parameters.

Cone beam CT doses in radiotherapy patient positioning in Finland-prostate treatments.

Imaging parameters, frequencies and resulting patient organ doses in treatments of prostate cancer were assessed in Finnish radiotherapy centres. Based on a questionnaire to the clinics, Monte Carlo method was used to estimate organ doses in International Commission on Radiological Protection standard phantom for prostate, bladder, rectum and femoral head. The results show that doses from cone beam computed tomography imaging have reduced compared to earlier studies and are between 3.6 and 34.5 mGy per image for the above-mentioned organs and for normal sized patients. There still is room for further optimization of the patient exposure, as many centres use the default imaging parameters, and the length of the imaged region may not be optimal for the purpose.

Feasibility of the partial-single arc technique in RapidArc planning for prostate cancer treatment.

The volumetric modulated arc therapy (VMAT) technique, in the form of RapidArc, is widely used to treat prostate cancer. The full-single arc (f-SA) technique in RapidArc planning for prostate cancer treatment provides efficient treatment, but it also delivers a higher radiation dose to the rectum. This study aimed to compare the dosimetric results from the new partial-single arc (p-SA) technique with those from the f-SA technique in RapidArc planning for prostate cancer treatment. In this study, 10 patients with low-risk prostate cancer were selected. For each patient, two sets of RapidArc plans (f-SA and p-SA) were created in the Eclipse treatment planning system. The f-SA plan was created using one full arc, and the p-SA plan was created using planning parameters identical to those of the f-SA plan but with anterior and posterior avoidance sectors. Various dosimetric parameters of the f-SA and p-SA plans were evaluated and compared for the same target coverage and identical plan optimization parameters. The f-SA and p-SA plans showed an average difference of ±1% for the doses to the planning target volume (PTV), and there were no clear differences in dose homogeneity or plan conformity. In comparison to the f-SA technique, the p-SA technique reduced the doses to the rectum by approximately 6.1% to 21.2%, to the bladder by approximately 10.3% to 29.5%, and to the penile bulb by approximately 2.2%. In contrast, the dose to the femoral heads, the integral dose, and the number of monitor units were higher in the p-SA plans by approximately 34.4%, 7.7%, and 9.2%, respectively. In conclusion, it is feasible to use the p-SA technique for RapidArc planning for prostate cancer treatment. For the same PTV coverage and identical plan optimization parameters, the p-SA technique is better in sparing the rectum and bladder without compromising plan conformity or target homogeneity when compared to the f-SA technique.

A RapidArc planning strategy for prostate with simultaneous integrated boost.

Since the clinical implementation of novel rotational forms of intensity-modulated radiotherapy, a variety of planning studies have been published that reinforce the major selling points of the technique. Namely, comparable or even improved dose distributions with a reduction in both monitor units and treatment times, when compared with static gantry intensity-modulated radiotherapy. Although the data are promising, a rigorous approach to produce these plans has yet to be established. As a result, this study outlines a robust and streamlined planning strategy with a concentration on RapidArc class solutions for prostate with a simultaneous integrated boost. This planning strategy outlines the field setup, recommended starting objectives, required user interactions to be made throughout optimization and post-optimization adjustments. A comparative planning study, with static gantry IMRT, is then presented as justification for the planning strategy itself. A variety of parameters are evaluated relating to both the planning itself (optimization and calculation time) and the plans that result. Results of this comparative study are in line with previously published data, and the planning process is streamlined to a point where the RapidArc optimization time takes 15 ± 1.3 minutes. Application of this planning strategy reduces the dependence of the produced plan on the experience of the planner, and has the potential to streamline the planning process within radiotherapy departments.

Helical tomotherapy significantly reduces dose to normal tissues when compared to 3D-CRT for locally advanced rectal cancer.

Combined modality treatment (neoadjuvant chemoradiotherapy followed by surgery) for locally advanced rectal cancer requires special attention to various organs at risk (OAR). As a result, the use of conformal dose delivery methods has become more common in this disease setting. Helical tomotherapy is an image-guided intensity modulated delivery system that delivers dose in a fan-beam manner at 7 degree intervals around the patient and can potentially limit normal tissue from high dose radiation while adequately treating targets. In this study we dosimetrically compare helical tomotherapy to 3D-CRT for stage T3 rectal cancer. The helical tomotherapy plans were optimized in the TomoPlan system to achieve an equivalent uniform dose of 45 Gy for 10 patients with T3N0M0 disease that was at least 5cm from the anal verge. The GTV included the rectal thickening and mass evident on colonoscopy and CT scan as well as with the help of a colorectal surgeon. The CTV included the internal iliac, obturator, and pre-sacral lymphatic chains. The OAR that were outlined included the small bowel, pelvic bone marrow, femoral heads, and bladder. Anatom-e system was used to assist in delineating GTV, CTV and OAR. These 10 plans were then duplicated and optimized into 3-field 3D-CRT plans within the Pinnacle planning system.The V[45], V[40], V[30], V[20], V[10], and mean dose to the OAR were compared between the helical tomotherapy and 3D-CRT plans. Statistically significant differences were achieved in the doses to all OAR, including all volumes and means except for V[10] for the small bowel and the femoral heads. Adequate dosimetric coverage of targets were achieved with both helical tomotherapy and 3D-CRT. Helical tomotherapy reduces the volume of normal tissue receiving high-dose RT when compared to 3D-CRT treatment. Both modalities adequately dose the tumor. Clinical studies addressing the dosimetric benefits are on-going.

RapidArc volumetric modulated therapy planning for prostate cancer patients.

PURPOSE: Recently, Varian Medical Systems have announced the introduction of a new treatment technique, RapidArc, in which dose is delivered over a single gantry rotation with dynamically variable MLC positions, dose rate and gantry speed. At Rigshospitalet, the RapidArc technique was brought into clinical practice in May 2008 for treatment of prostate cancer patients. We report here our experiences with performing treatment planning using the Eclipse RapidArc optimization software for this patient group. MATERIAL AND METHODS: A stand-alone installation of Eclipse 8.5 with RapidArc optimization capability was performed at Rigshospitalet. Patient data for 8 prostate cancer patients were imported, most of whom were previously treated at Rigshospitalet using IMRT. Three of the patients were treated at Rigshospitalet using the RapidArc technique. Treatment plans were optimized using objectives as given by standard guidelines for clinical treatment planning. RapidArc plans were compared to the IMRT plans by which the patients were actually treated or in the three cases treated with the RapidArc technique to IMRT plans achieved using standard guidelines. Comparison was done with respect to target coverage, doses to rectum and bladder, over-all maximum dose and number of monitor units. RESULTS: Overall, the RapidArc treatment plans gave better or equal sparing of the organs at risk than the IMRT treatment plans. The number of monitor units was lower in most cases, by up to approximately 75%. However, the target dose homogeneity was not as high as for IMRT. The low-dose bath was larger than for IMRT. CONCLUSION: RapidArc optimization is very promising, especially regarding the potential of reducing the number of monitor units, while providing good sparing of organs at risk. Some improvement is still warranted with respect to achieving high target dose homogeneity.

Magnetic resonance imaging radiomic feature analysis of radiation-induced femoral head changes in prostate cancer radiotherapy.

BACKGROUND AND PURPOSE: As a feasible approach, radiotherapy has a great role in prostate cancer (Pca) management. However, Pca patients have an increased risk of femoral head damages including fractures after radiotherapy. The mechanisms of these complications are unknown and time of manifestations is too long; however, they may be predicted by early imaging. The main purpose of this study was to assess the early changes in femoral heads in Pca patients treated with intensity-modulated radiation therapy (IMRT) using multiparametric magnetic resonance imaging (mpMRI) radiomic feature analysis. MATERIALS AND METHODS: Thirty Pca patients treated with IMRT were included in the study. All patients underwent two mpMRI pre- and postradiotherapy. Thirty-four robust radiomic features were extracted from T1, T2, and apparent diffusion coefficient (ADC) obtained from diffusion-weighted images. Wilcoxon signed-rank test was performed to assess the significance of the change in the mean T1, T2, and ADC radiomic features postradiotherapy relative to preradiotherapy values. The percentage change values were normalized based on the natural logarithm base ten. Features were also ranked based on their median changes. RESULTS: Sixty femoral heads were analyzed. All radiomic features have undergone changes. Significant postradiotherapy radiomic feature changes were observed in 20 and 5 T1- and T2-weighted radiomic features, respectively (P < 0.05). ADC features did not vary significantly postradiotherapy. The mean radiation dose received by femoral heads was 40 Gy. No fractures were observed within the follow-up time. Different features were found as high ranked among T1, T2, and ADC images. CONCLUSION: Early structural change analysis using radiomic features may contribute to predict postradiotherapy fracture in Pca patients. These features can be identified as being potentially important imaging biomarkers for predicting radiotherapy-induced femoral changes.

Investigation of differences of sacral and vertebral bone mineral densities before and after radiotherapy in patients with locally advanced rectal cancer.

PURPOSE: Radiotherapy is a treatment method performed using ionizing radiation on cancer patients either alone or with surgery and/or chemotherapy. Although modern radiotherapy techniques provide a significant advantage in protecting healthy tissues, it is inevitable that normal tissues are also located in the areas targeted by radiations. In this study, we aimed to examine the bone mineral density changes in bone structures commonly included in the irradiated area such as, L5 vertebra, sacrum, and femur heads, in patients who have received pelvic radiotherapy; and the relationship between these changes with radiation dose. MATERIAL AND METHODS: Patients included in the study had been previously diagnosed with rectal cancer, which were operated or not. Preoperative or postoperative pelvic radiotherapy was planned for all patients. In terms of convenience when comparing with future scans, all densitometry and CT scans were performed with the same devices. Fifteen patients were included in the study. In order to determine the dose of radiation each identified area had taken after radiotherapy, the sacrum, L5 vertebra, bilateral femoral heads, and L1 regions were contoured in the CT scans in which treatment planning was done. Sagittal cross-sectional images were taken advantage of while these regions were being contoured. RESULTS: Bone mineral density was evaluated with CT and dual-energy X-ray absorptiometry before and after the treatment. The regions that have theoretically been exposed to irradiation, such as L5, sacrum, left to right femur were found to have significant difference in terms of bone density. According to CT evaluation, there was a significant decrease in bone intensity of L5, sacrum, left and right femurs. Dual-energy X-ray absorptiometry assessment revealed that the whole of the left femoral head, left femur neck and Ward's region were significantly affected by radiotherapy. However, there was no significant difference in the sacrum and L5 vertebra before and after radiotherapy. CONCLUSION: More accurate results could be achieved if the same study was conducted on a larger patient population, with a longer follow-up period. When the reduction in bone density is at maximum or a cure is likely in a long-term period, bone mineral density could be determined by measurements performed at regular intervals.

Comparison of Deep Learning-Based and Patch-Based Methods for Pseudo-CT Generation in MRI-Based Prostate Dose Planning.

PURPOSE: Deep learning methods (DLMs) have recently been proposed to generate pseudo-CT (pCT) for magnetic resonance imaging (MRI) based dose planning. This study aims to evaluate and compare DLMs (U-Net and generative adversarial network [GAN]) using various loss functions (L2, single-scale perceptual loss [PL], multiscale PL, weighted multiscale PL) and a patch-based method (PBM). METHODS AND MATERIALS: Thirty-nine patients received a volumetric modulated arc therapy for prostate cancer (78 Gy). T2-weighted MRIs were acquired in addition to planning CTs. The pCTs were generated from the MRIs using 7 configurations: 4 GANs (L2, single-scale PL, multiscale PL, weighted multiscale PL), 2 U-Net (L2 and single-scale PL), and the PBM. The imaging endpoints were mean absolute error and mean error, in Hounsfield units, between the reference CT (CTref) and the pCT. Dose uncertainties were quantified as mean absolute differences between the dose volume histograms (DVHs) calculated from the CTref and pCT obtained by each method. Three-dimensional gamma indexes were analyzed. RESULTS: Considering the image uncertainties in the whole pelvis, GAN L2 and U-Net L2 showed the lowest mean absolute error (≤34.4 Hounsfield units). The mean errors were not different than 0 (P ≤ .05). The PBM provided the highest uncertainties. Very few DVH points differed when comparing GAN L2 or U-Net L2 DVHs and CTref DVHs (P ≤ .05). Their dose uncertainties were ≤0.6% for the prostate planning target Volume V95%, ≤0.5% for the rectum V70Gy, and ≤0.1% for the bladder V50Gy. The PBM, U-Net PL, and GAN PL presented the highest systematic dose uncertainties. The gamma pass rates were >99% for all DLMs. The mean calculation time to generate 1 pCT was 15 s for the DLMs and 62 min for the PBM. CONCLUSIONS: Generating pCT for MRI dose planning with DLMs and PBM provided low-dose uncertainties. In particular, the GAN L2 and U-Net L2 provided the lowest dose uncertainties together with a low computation time.

A treatment planning study comparing volumetric arc modulation with RapidArc and fixed field IMRT for cervix uteri radiotherapy.

PURPOSE: A treatment planning study was performed to evaluate the performance of the novel volumetric modulated single arc radiotherapy on cervix uteri cancer patients. Conventional fixed field IMRT was used as benchmark. METHODS AND MATERIALS: CT datasets of eight patients were included in the study. Plans were optimised with the aim to assess organs at risk and healthy tissue sparing while enforcing highly conformal target coverage. Planning objectives for PTV were: maximum significant dose lower than 52.5 Gy and minimum significant dose higher than 47.5 Gy. For organs at risk, the median and maximum doses were constrained to be lower than 30 (rectum), 35 (bladder) and 25 Gy (small bowel) and 47.5 Gy; additional objectives were set on various volume thresholds. Plans were evaluated on parameters derived from dose volume histograms and on NTCP estimates. Peripheral doses at 5, 10 and 15 cm from the PTV surface were recorded to assess the low-level dose bath. The MU and delivery time were scored to measure expected treatment efficiency. RESULTS: Both RapidArc and IMRT resulted in equivalent target coverage but RapidArc had an improved homogeneity (D(5%)-D(95%) = 3.5 +/- 0.6 Gy for RapidArc and 4.3 +/- 0.8 Gy for IMRT) and conformity index (CI(90%) = 1.30 +/- 0.06 for RapidArc and 1.41 +/- 0.15 for IMRT). On rectum the mean dose was reduced by about 6 Gy (10 Gy for the rectum fraction not included in the PTV). Similar trends were observed for the various dose levels with reductions ranging from approximately 3 to 14.4 Gy. For the bladder, RapidArc allowed a reduction of mean dose ranging from approximately 4 to 6Gy and a reduction from approximately 3 to 9 Gy w.r.t. IMRT. Similar trends but with smaller absolute differences were observed for the small bowel and left and right femur. NTCP calculations on bladder and rectum confirmed the DVH data with a potential relative reduction ranging from 30 to 70% from IMRT to RapidArc. The healthy tissue was significantly less irradiated in the medium to high dose regions (from 20 to 30 Gy) and the integral dose reduction with RapidArc was about 12% compared to IMRT. Concerning peripheral dose, the relative difference between IMRT and RapidArc was of 9 +/- 2%, 43 +/- 11% and 36 +/- 5% at 5, 10 and 15 cm from the PTV surface, respectively. The MU/Gy from RapidArc was 245 +/- 17 corresponding to an expected average beam on time of 73 +/- 10 s per fractions of 2 Gy. IMRT plans presented higher values with an average of MU/Gy = 479 +/- 63. CONCLUSION: RapidArc was investigated for cervix uteri cancer showing significant improvements in organs at risk and healthy tissue sparing with uncompromised target coverage leading to better conformal avoidance of treatments w.r.t. conventional IMRT. This, in combination with the confirmed short delivery time, can lead to clinically significant advances in the management of this highly aggressive cancer type. Clinical protocols are now advised to evaluate prospectively the potential benefit observed at the planning level.

Comparison of dose contribution to normal pelvic tissues among conventional, conformal and intensity-modulated radiotherapy techniques in prostate cancer.

High-energy external radiotherapy has become one of the most common treatment in localized prostate cancer. We compared the difference of dose distribution, mainly at the 5-30 Gy dose level, in the irradiated pelvic volume among three modalities of radiotherapy for patients with prostate cancer: conventional, conformal and intensity-modulated radiotherapy (IMRT). We selected six patients with prostate cancer treated by conformal radiotherapy at the doses of 46 Gy to PTVN (prostate and seminal vesicles), and 70 Gy to PTV-T (prostate). The conventional technique": an 8-field arrangement was used; the conformal technique 4 fields with a boost through 6 fields. For IMRT, a five-beam arrangement was used. Dose-volume histograms (DVH) were analyzed and compared among the three techniques. The IMRT technique significantly increased the pelvic volume covered by the isodose surfaces below 15 Gy as compared with the conventional and conformal techniques. The mean absolute increase for the pelvic volume included between 5-30 Gy for the IMRT technique, was about 2 900 ml as compared with the conventional technique. However, IMRT significantly reduced the irradiated volume of the rectum in the dose range of 5 to 40 Gy, also significantly reduced the irradiated volume of bladder and femoral heads, and obtained a similar or improved isodose distribution in the PTVs. In addition, the use of IMRT slightly increased the relative dose delivered to the body volume outside the pelvis, as estimated by the use of specific software. A long-term follow-up will be needed to evaluate potential late treatment complications related to the use of IMRT and the low or moderate irradiation dose level obtained in the pelvis and in the whole body.

[Formation of ossification nucleus in the femoral head in hamsters exposed to laser radiation].

The purpose of the study was to detect the relation between the formation of ossification nucleus in the epiphysis and the ingrowth of vessels into it, using laser radiation of femoral heads. The study was performed in 30 golden hamsters, 20 of them starting at 10 days after birth were exposed to daily irradiation of the right hip joint (during 3-80 days). The left joint was used as control. The radiation was performed with Agnis laser device (radiation power--2 mW, impulse frequency--2500 Hz, exposure duration--8 min, optical fiber diameter--4 mm). Femoral bones of experimental and control animals were histologically studied at days 13 till 90. Laser radiation was found could delay vessel growth from diaphysis into epiphysis for up to 13 days, and the beginning of ossification nucleus formation in the femoral head--for up to 5 days. This suggests the direct relation of the development of bone ossification nucleus in the epiphysis and growing of vessels into its cartilage, since no other factors retarding the vessel growth and formation of bone nucleus were used.

Efficiently train and validate a RapidPlan model through APQM scoring.

PURPOSE: The aim of this study was to propose and validate an intuitive method for training and to validate knowledge-based planning (KBP) systems based on a patient-specific plan quality scoring. METHODS: A sample of 80 clinical plans of prostate cancer patients were ranked on the basis of the Adjusted Plan Quality Metric (APQM%). This quality metric was computed normalizing the Plan Quality Metric (PQM%) score to the best possible OAR sparing estimated by the Feasibility DVH (FDVH) algorithm. Two different plan libraries were created, purging all the plans below the first quartile or below the median the APQM% distribution. These libraries were used to populate and train two RapidPlan models: respectively, the APMQ25% and the APMQ50% models. No further refinements or actions were undertaken on these two models. Their performances were benchmarked against another two RapidPlan models. An Uncleaned model, which was populated and trained with the initial sample of 80 plans, and a Cleaned model, obtained through the standard iterative cleaning and refinement process suggested by the vendor and in literature. The outcomes of a planning test based on 20 patients within the training library (closed loop) and 20 patients outside of the training library (open-loop) were compared through various DVH metrics and the PQM% score. RESULTS: The selection through APQM% thresholding roughly preserves the geometric variety of the Cleaned model; only the APMQ50% model showed a modest broadness reduction. The models generated through APQM% thresholding showed target coverage and OARs sparing equal or superior to the Uncleaned and Cleaned models both for the closed- and the open-loop tests. No significant differences were found between the four models. PQM% analysis ranked the overall plan quality as: 86.5 ± 6.5% APQM50% , 83.1 ± 5.9% APQM25% , 80.39 ± 10.6% Cleaned and 79.4 ± 8.5% Uncleaned in the closed-loop test; 84.9 ± 7.6% APQM50% , 82.6 ± 7.9% APQM25% , 80.39 ± 10.6% Cleaned and 79.4 ± 8.5% Uncleaned in the open-loop test. CONCLUSIONS: Forward feeding a RapidPlan model through a thresholding selection based on APQM% is proven to produce equal or better results than a model based on a manually and iteratively refined population. A tighter APQM% threshold turns approximately into a higher average quality of plans generated with RapidPlan. A trade-off must be found between the mean quality of the KBP library and its numerosity. The proposed KBP feeding method helps the KBP user, because it makes the model refinement more intuitive and less time consuming.

Quantifying the performance of two different types of commercial software programs for 3D patient dose reconstruction for prostate cancer patients: Machine log files vs. machine log files with EPID images.

We clarified the reconstructed 3D dose difference between two different commercial software programs (Mobius3D v2.0 and PerFRACTION v1.6.4). Five prostate cancer patients treated with IMRT (74 Gy/37 Fr) were studied. Log files and cine EPID images were acquired for each fraction. 3D patient dose was reconstructed using log files (Mobius3D) or log files with EPID imaging (PerFRACTION). The treatment planning dose was re-calculated on homogeneous and heterogeneous phantoms, and log files and cine EPID images were acquired. Measured doses were compared with the reconstructed point doses in the phantom. Next, we compared dosimetric metrics (mean dose for PTV, rectum, and bladder) calculated by Mobius3D and PerFRACTION for all fractions from five patients. Dose difference at isocenter between measurement and reconstructed dose for two software programs was within 3.0% in both homogeneous and heterogeneous phantoms. Moreover, the dose difference was larger using skip arc plan than that using full arc plan, especially for PerFRACTION (e.g., dose difference at isocenter for PerFRACTION: 0.34% for full arc plan vs. -4.50% for skip arc plan in patient 1). For patients, differences in dosimetric parameters were within 1% for almost all fractions. PerFRACTION had wider range of dose difference between first fraction and the other fractions than Mobius3D (e.g., maximum difference: 0.50% for Mobius3D vs. 1.85% for PerFRACTION), possibly because EPID may detect some types of MLC positioning errors such as miscalibration errors or mechanical backlash which cannot be detected by log files, or that EPID data might include image acquisition failure and image noise.

Patient Reported Outcomes in NRG Oncology RTOG 0938, Evaluating Two Ultrahypofractionated Regimens for Prostate Cancer.

PURPOSE: There is considerable interest in very short (ultrahypofractionated) radiation therapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience, and resource allocation benefits. Our objective is to demonstrate that detectable changes in health-related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline scores. METHODS AND MATERIALS: NRG Oncology's RTOG 0938 is a nonblinded randomized phase 2 study of National Comprehensive Cancer Network low-risk prostate cancer in which each arm is compared with a historical control. Patients were randomized to 5 fractions (7.25 Gy in 2 weeks) or 12 fractions (4.3 Gy in 2.5 weeks). The co-primary endpoints were the proportion of patients with a change in EPIC-50 bowel score at 1 year (baseline to 1 year) >5 points and in EPIC-50 urinary score >2 points tested with a 1-sample binomial test. RESULTS: The study enrolled 127 patients to 5 fractions (121 analyzed) and 128 patients to 12 fractions (125 analyzed). Median follow-up for all patients at the time of analysis was 3.8 years. The 1-year frequency for >5 point change in bowel score were 29.8% (P < .001) and 28.4% (P < .001) for 5 and 12 fractions, respectively. The 1-year frequencies for >2 point change in urinary score were 45.7% (P < .001) and 42.2% (P < .001) for 5 and 12 fractions, respectively. For 5 fractions, 32.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥11 points (P = .34); for 12 fractions, 30.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥ 11 points (P = .20). Disease-free survival at 2 years is 99.2% (95% confidence interval: 97.5-100) in the 5-fraction arm and 97.5% (95% confidence interval: 94.6-100) in the 12-fraction arm. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity. CONCLUSIONS: This study confirms that, based on changes in bowel and urinary domains and toxicity (acute and late), the 5- and 12-fraction regimens are well tolerated. These ultrahypofractionated approaches need to be compared with current standard radiation therapy regimens.

Long-term results of acetabular reconstruction using irradiated allograft bone.

AIMS: The management of acetabular defects at the time of revision hip arthroplasty surgery is a challenge. This study presents the results of a long-term follow-up study of the use of irradiated allograft bone in acetabular reconstruction. PATIENTS AND METHODS: Between 1990 and 2000, 123 hips in 110 patients underwent acetabular reconstruction for aseptic loosening, using impaction bone grafting with frozen, irradiated, and morsellized femoral heads and a cemented acetabular component. A total of 55 men and 55 women with a mean age of 64.3 years (26 to 97) at the time of revision surgery are included in this study. RESULTS: At a mean follow-up of 16.9 years, there had been 23 revisions (18.7%), including ten for infection, eight for aseptic loosening, and three for dislocation. Of the 66 surviving hips (58 patients) that could be reassessed, 50 hips (42 patients; 75.6%) were still functioning satisfactorily. Union of the graft had occurred in all hips with a surviving implant. Survival analysis for all indications was 80.6% at 15 years (55 patients at risk, 95% confidence interval (CI) 71.1 to 87.2) and 73.7% at 20 years (eight patients at risk, 95% CI 61.6 to 82.5). CONCLUSION: Acetabular reconstruction using frozen, irradiated, and morsellized allograft bone and a cemented acetabular component is an effective method of treatment. It gives satisfactory long-term results and is comparable to other types of reconstruction. Cite this article: Bone Joint J 2018;100-B:1449-54.

Treatment-planning study of prostate cancer intensity-modulated radiotherapy with a Varian Clinac operated without a flattening filter.

PURPOSE: To assess the feasibility of intensity-modulated radiotherapy for prostate cancer using photon beams from an accelerator operated without a flattening filter; and to determine potential benefits and drawbacks of using unflattened beams for this type of treatment. METHODS AND MATERIALS: Intensity-modulated radiotherapy plans were generated for 10 patients with early-stage prostate cancer. For each patient, four plans were generated: with and without the flattening filter, at 6 and 18 MV. The prescription dose was 75.6 Gy to 98% of the planning target volume. The number of beams, their orientations, and optimization constraints were the same for all plans. Plans were generated with Eclipse 8.0 (Varian Medical Systems). RESULTS: All the plans developed with unflattened beams were clinically acceptable. In terms of patient dose distributions, plans with unflattened beams were similar to the corresponding plans with flattened beams. Plans with unflattened beams required fewer monitor units (MUs) per plan: on average, by a factor of 2.0 at 6 MV and 2.6 at 18 MV, assuming that removal of the flattening filter was not followed by recalibration of MUs. CONCLUSIONS: Clinically acceptable intensity-modulated radiotherapy plans for prostate cancer can be developed with unflattened beams at both 6 and 18 MV. Dosimetrically, flattened and unflattened beams generated similar treatment plans. The plans with unflattened beams required substantially fewer MUs. The reduction in the number of MUs indicates corresponding reduction in beam-on time and in the amount of radiation outside the target.