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Background : Respiratory motion management with breath hold for patients with hepatobiliary cancers remains a challenge in the precise positioning for radiotherapy. We compared different image-guided alignment markers for estimating positional errors, and investigated the factors associated with positional errors under breath-hold control. Methods : Spirometric motion management system (SDX) for breath holds was used in 44 patients with hepatobiliary tumor. Among them, 28 patients had a stent or embolized materials (lipiodol) as alignment markers. Cone-beam computed tomography (CBCT) and kV-orthogonal images were compared for accuracy between different alignment references. Breath-hold level (BHL) was practiced, and BHL variation (ΔBHL) was defined as the standard deviation in differences between actual BHLs and baseline BHL. Mean BHL, ΔBHL, and body-related factors were analyzed for the association with positional errors. Results : Using the reference CBCT, the correlations of positional errors were significantly higher in those with stent/lipiodol than when the vertebral bone was used for alignment in three dimensions. Patients with mean BHL >1.4 L were significantly taller (167.6 cm vs. 161.6 cm, p=0.03) and heavier (67.1 kg vs. 57.4 kg, p=0.02), and had different positional error in the craniocaudal direction (-0.26 cm [caudally] vs. +0.09 cm [cranially], p=0.01) than those with mean BHL 0.03 L. Conclusion : Under rigorous breath-hold respiratory control, BHL correlated with body weight and height. With more accurate alignment reference by stent/lipiodol, actual BHL but not breath-hold variation was associated with craniocaudal positional errors.

Additional file 1: Supplementary Figure 1. (A) Training and preparation sessions of SDX system included (a) the determination of the inspiratory capacity and (b) the selection of the volumetric value. (c) The breath-hold level was defined as 85% of the inspiratory capacity and (d) the breath-hold range was restricted within 0.1 L. (B) During real treatment, patients were instructed by traffic light icon to distinguish (a) non-breath-hold phase (beam off) and (b) breath-hold phase (beam on).

Purpose To identify various dosimetric parameters of bone marrow cavity that correlate with acute hematologic toxicity (HT) in patients with anal squamous cell carcinoma treated with definitive chemoradiation therapy (CRT). Methods and materials We analyzed 32 patients receiving CRT. The whole pelvic bone marrow (PBM) and the lumbosacral spine (LSS) subregion were contoured for each patient. Marrow cavities were contoured using the Hounsfield units (HUs) of 100, 150, 200, and 250 as maximum density threshold levels. The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. The endpoint was grade ≥3 HT (HT3+). Normal-tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Maximal likelihood estimate was used to compare the parameter set. Logistic regression was used to test associations between HT and both dosimetric and clinical parameters. Results Ten patients (31%) experienced HT3+. While dose to both LSS and PBM significantly predicted for HT3+, LSS was superior to PBM by logistic regression and LKB modeling. Constrained optimization of the LKB model for HT3+ yielded the parameters m=0.21, n=1, and TD 50 = 32 Gy for LSS. The NTCP fits were better with the whole bone than with marrow cavity using any HU threshold. Mean LSS doses of 21 Gy and 23.5 Gy result in a 5% and 10% risk of HT3+, respectively. Mean dose and low-dose radiation parameters (V5, V10, V15, V20) of whole bone or bone cavities of LSS were correlated most significantly with HT3+. Conclusions For predicting the risk of HT3+, whole-bone contours were superior to marrow cavity and LSS was superior to PBM by LKB modeling. The results confirm PBM and LSS as parallel organs when predicting hematologic toxicity. Recommended dose constraints to the LSS are V10 ≤80%. An LSS mean dose of 23.5 Gy is associated with a 10% risk of HT.

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.

To investigate the unexpected skin dose increase from intensity-modulated radiation therapy (IMRT) on vacuum cushions and carbon-fiber couches and then to modify the dosimetric plan accordingly. Eleven prostate cancer patients undergoing IMRT were treated in prone position with a vacuum cushion. Two under-couch beams scattered the radiation from the vacuum cushion and carbon-fiber couch. The IMRT plans with both devices contoured were compared with the plans not contouring them. The skin doses were measured using thermoluminescent dosimeters (TLDs) placed on the inguinal regions in a single IMRT fraction. Tissue equivalent thickness was transformed for both devices with the relative densities. The TLD-measured skin doses (59.5 +/- 9.5 cGy and 55.6 +/- 5.9 cGy at left and right inguinal regions, respectively) were significantly higher than the calculated doses (28.7 +/- 4.7 cGy; p = 2.2 x 10(-5) and 26.2 +/- 4.3 cGy; p = 1.5 x 10(-5)) not contouring the vacuum cushion and carbon-fiber couch. The calculated skin doses with both devices contoured (59.1 +/- 8.8 cGy and 55.5 +/- 5.7 cGy) were similar to the TLD-measured doses. In addition, the calculated skin doses using the vacuum cushion and a converted thickness of the simulator couch were no different from the TLD-measured doses. The recalculated doses of rectum and bladder did not change significantly. The dose that covered 95% of target volume was less than the prescribed dose in 4 of 11 patients, and this problem was solved after re-optimization applying the corrected contours. The vacuum cushion and carbon-fiber couch contributed to increased skin doses. The tissue-equivalent-thickness method served as an effective way to correct the dose variations.

Background and purpose Cone-beam computed tomography (CBCT) increases the doses on normal tissues. Our study sought to develop a mathematical model that would provide an estimate of and verify in vivo rectal dose from CBCT in prostate cancer patients. Materials and methods Thermoluminescent dosimeters (TLDs) and Rando phantoms were used to measure doses to the pelvic region. We used an endorectal balloon to measure rectal doses for 10 prostate cancer patients who underwent radiotherapy and for whom we were able to acquire CBCT images. A solid water phantom and TLDs were used to correlate the rectal doses with body thickness/widths. A mathematical method was established to simulate the dose to which the patient is exposed during CBCT for the determined body parameters. The estimated doses were compared with the measured doses to determine the effectiveness of the model. Results The average measured rectal dose from CBCT was 2.8 ± 0.3 cGy. The mathematical method was able to predict the rectal dose, with the limits of agreement of −0.03 ± 0.18 cGy. The average difference between predictions and measurements was −1.1 ± 3.6%. Conclusion Our mathematical model was effective in estimating the exposed dose from CBCT.

To investigate the association between clinical/dosimetric factors and postoperative pulmonary complications (PPC) in esophageal cancer patients undergoing neoadjuvant chemotherapy and intensity-modulated radiation therapy (IMRT) followed by thoracic esophagectomy. The data from 52 patients receiving combined modality treatment were analyzed. Chemotherapy was taxane-based in 43 and 5-fluorouracil-based in 9 patients. IMRT (40–45 Gy, median 40 Gy, at 1.8–2 Gy per fraction) was given using a 3–5-beam arrangement. Surgery consisted of open or minimally invasive esophagectomy. The dosimetric parameters were generated from lung dose-volume histogram computed by the treatment planning software. PPC was defined as pneumonia or respiratory insufficiency within 30 days after surgery. Statistical correlations were analyzed between clinical/dosimetric factors and PPC. The incidence of PPC was 34.6%. No patients died of PPC. Two patients (3.8%) became ventilator dependent. In univariate analyses, preoperative forced expiratory volume in 1 s (FEV1) and forced vital capacity before surgery were significantly associated with PPC (P = 0.02 and 0.04, respectively). None of the dosimetric factors predicted development of PPC. For the 51 patients undergoing right transthoracic surgery, higher absolute spared volume of the right lung receiving 15 Gy was significantly associated with PPC (P = 0.03). In multivariate analysis, preoperative FEV1 was the only independent factor associated with PPC (P = 0.002). Preoperative rather than prechemoradiation FEV1 predicts development of PPC. Reducing the absolute volume of the right lung that is irradiated might decrease the risk of PPC for patients receiving right transthoracic surgery.

Linear accelerators equipped with X-ray volumetric cone-beam Imaging (XVI) system enable verification of location of patients and displacement of tumors for image-guided radiotherapy (IGRT). The objective of this study is to evaluate the positioning accuracy using the XVI system for image-guided patient setup and to establish a lower-dose imaging protocol without sacrificing positioning accuracy for routine treatment courses. Several low-dose imaging protocols are proposed by modifying tube voltage from 120 to 100 kV and lowering tube current from 40 to 10 mA. The positioning accuracy of both bone and gray value registration methods provided by XVI system were also evaluated. Phantom study revealed that the gray value algorithm was more accurate than the bone algorithm in position and registration. However, both translational and rotational accuracies were less than 0.15 mm and 0.8 ° at all dimensions, which were considered negligible in clinical applications. In addition, the lower-dose protocol (100 kV, 10 mA) produced relative much less radiation dose compared to the default CBCT protocol in the XVI system. In conclusion, our proposed lower-dose protocol results in significant radiation dose reduction without compromising positioning accuracy and may have the potential to be adopted for clinical usage in the future.

To include biologic factors in parallel-architecture normal-tissue complication probability (NTCP) model for radiation-induced liver disease (RILD) after three-dimensional conformal radiotherapy (3D-CRT) for gastric or hepatic cancer.A total of 151 patients (89 with hepatocellular carcinoma and 62 with gastric cancer) who received 3D-CRT to the liver were included (isocenter dose range 33.0 to 66.0 Gy; mean 48.0 Gy). RILD was defined as grade 3 or higher liver toxicity according to Common Toxicity Criteria Version 2.0 of the National Cancer Institute within 4 months after 3D-CRT. Possible correlations of patient-related or dosimetric factors with RILD were tested. Maximum-likelihood analysis estimated NTCP model parameters for group and subgroups. Goodness-of-fit analysis estimated deviance of NTCP model parameters between subgroups.RILD developed in 25 patients. Hepatitis B virus carrier status (p0.001) was the only significant independent factor. The 4 parallel NTCP model parameters, mean functional reserve (V(50)), width of functional reserve distribution (sigma), dose damage to 50% of liver subunits (D(50)), and slope parameter for subunit dose-response (k), were respectively, 0.54, 0.14, 50 Gy, 0.18 (group); 0.53, 0.07, 50 Gy, 4.6 x 10(-7) (carriers); 0.59, 0.12, 25 Gy, 59.8 (noncarriers). In carrier-state subgroups, goodness-of-fit deviance with 1 subgroup's parameter set would have been worse in the other group. Across subgroups, patients with RILD all had liver fraction damage (f) greater than 0.4 compared with wider distribution for the whole group.RILD is described with a parallel-architecture NTCP model for HBV carriers and noncarriers with a threshold effect greater than 0.4. The main difference is in slope parameter for subunit dose-response.

Purpose: To identify the factors associated with radiation-induced liver disease (RILD) and to describe the difference in normal tissue complication probability (NTCP) between subgroups of hepatocellular carcinoma patients undergoing three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: A total of 89 hepatocellular carcinoma patients who completed 3D-CRT for local hepatic tumors were included. The average isocenter dose was 49.9 ± 6.2 Gy. Logistic regression analysis was used for the association between statistically significant factors and RILD (defined as Grade 3 or 4 hepatic toxicity of elevated transaminases or alkaline phosphatase within 4 months of completing 3D-CRT) in multivariate analysis. Maximal likelihood analysis was conducted to obtain the best estimates of the NTCP model parameters. Results: Of the 89 patients, 17 developed RILD. In univariate analysis, hepatitis B virus (HBV)-positive status and the mean radiation dose to the liver were the two factors significantly associated with the development of RILD. Of the 65 patients who were HBV carriers, 16 had RILD compared with 1 of 24 non–carrier patients ( p = 0.03). The mean radiation dose to liver was significantly greater in patients with RILD (22.9 vs. 19.0 Gy, p = 0.05). On multivariate analysis, HBV carrier status (odds ratio, 9.26; p = 0.04) and Child-Pugh B cirrhosis of the liver (odds ratio, 3.65; p = 0.04) remained statistically significant. The best estimates of the NTCP parameters were n=0.35, m=0.39, and TD 50 (1) = 49.4 Gy. The n, m, TD 50 (1) specifically estimated from the HBV carriers was 0.26, 0.40, and 50.0 Gy, respectively, compared with 0.86, 0.31, and 46.1 Gy, respectively, for non–carrier patients. Conclusion: Hepatocellular carcinoma patients who were HBV carriers or had Child-Pugh B cirrhosis presented with a statistically significantly greater susceptibility to RILD after 3D-CRT.

To estimate the respiration-induced dosimetric change at beam edge during a beam-on interval of radiotherapy, by the integration of a mathematical model for organ motion and a modeled beam profile. A method is proposed which incorporated the effects of intra-treatment organ motion due to breathing on the dosimetric change for the treatment of liver cancer. The basic algorithm was to assume the motion of infra-abdominal organs was predominantly in the superior-inferior (S-I) direction. The starting phase was defined as the mid-phase at exhale, to reproduce the same situation of computed tomography simulation for liver cancer. The S-I extent of motion was defined as 1.5cm. The period of a breathing cycle was defined as 4.2 seconds. The shape parameter of the respiratory model was defined as 3. The radiation dose of 100 cGy given with the rate of 300 MU/minute was designed for the model analysis. The position at the beam edge as a function of time could be parameterized for a 10cm x 10cm field with a setup of SAD 100cm. The dose profiles of both 6MV and 18MV photons were applied for the dosimetric calculation of the beam-edge point during the dynamic movement in a beam-on time interval of radiotherapy. The point doses at the superior beam edge for 6MV photons and18MV photons during a beam-one interval of 22.8 seconds were 73.5% and 77.2% of the isocenter dose, respectively. The point doses at the inferior beam edge for the two energies were 31.2% and 32.4%, respectively. There were 147-154% dose increase for superior beam edge and 62.4-64.8% dose decrease for inferior beam edge, as compared to the 50% isocenter dose with the static dose distribution. It is simple and feasible to use the mathematical model to estimate the dosimetric change of the intra-abdominal organ motion from respiration. The impact of respiration on the dosimetric difference deserves more attention in the prescription of radiation treatment. Further measurement of the exact organ motion during the real treatment is warranted to optimize the model.

We programmably divided long-arc volumetric modulated arc therapy (VMAT) into split short arcs, each taking less than 30 s for respiratory coordination. The VMAT plans of five pancreatic cancer patients were modified; the short-arc plans had negligible dose differences and satisfied the 3%/3-mm gamma index on a MapCHECK-2 device.

The accurate volumetric calculation of moving targets/organs is required to use cone-beam computed tomography (CBCT) for replanning purposes. This study was aimed to correct the reconstructed volume losses of moving phantoms by phase-specific CBCT.Planning fan-beam CT (FBCT) of five hepatobiliary/gastrointestinal/pancreatic cancer patients were acquired under active breathing control and compared with free-breathing CBCT for kidney volumes. Three different-sized ball phantoms were scanned by FBCT and CBCT. Images were imported to a planning system to compare the reconstructed volumes. The phantoms were moved longitudinally on an oscillator with different amplitudes/frequencies. The phase-specific projections of CBCT for moving phantoms were selected for volume reconstruction.The differences in reconstructed volumes of static small, medium, large phantoms between FBCT and CBCT were - 6.7%, - 2.3%, and - 2.0%, respectively. With amplitudes of 7.5-20 mm and frequencies of 8-16 oscillations/min, volume losses on CBCT were comparable with FBCT in large moving phantoms (range 9.1-27.2%). Amplitudes were more subject to volume losses than frequencies. On phase-specific CBCT, volume losses were reduced to 2.3-6.5% by reconstruction using 2-3 projections at end/midoscillation phase.Amplitude had more impact than frequency on volume losses of moving phantoms on CBCT. Phase-specific CBCT reduced volume losses.

Volumetric modulated arc therapy (VMAT), a novel technique, employs a linear accelerator to conduct dynamic modulation rotation radiotherapy. The goal of this study was to compare VMAT with helical tomotherapy (HT) and step-and-shoot intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) patients with regard to the sparing effect on organs at risk (OARs), dosimetric quality, and efficiency of delivery.Twenty patients with NPC treated by HT were re-planned by VMAT (two arcs) and IMRT (7-9 fields) for dosimetric comparison. The target area received three dose levels (70, 60, and 54 Gy) in 33 fractions using simultaneous integrated boosts technique. The Philips Pinnacle Planning System 9.0 was adopted to design VMAT, using SmartArc as the planning algorithm. For a fair comparison, the planning target volume (PTV) coverage of the 3 plans was normalized to the same level. Dosimetric comparisons between VMAT, HT, and IMRT plans were analyzed to evaluate (1) coverage, homogeneity, and conformity of PTV, (2) sparing of OARs, (3) delivery time, and (4) monitor units (MUs).The VMAT, HT, and IMRT plans had similar PTV coverage with an average of 96%. There was no significant difference between VMAT and HT in homogeneity, while the homogeneity indices of VMAT (1.06) and HT (1.06) were better than IMRT plans (1.07, p0.05). HT plans provided a better conformity index (1.17) than VMAT (1.28, p=0.01) and IMRT (1.36, p=0.02). When compared with IMRT, VMAT and HT had a better sparing effect on brain stem and spinal cord (p0.05). The effect of parotid sparing was similar between VMAT (mean=26.3 Gy) and HT (mean=27.5 Gy), but better than IMRT (mean=31.3 Gy, p0.01). The delivery time per fraction for VMAT (5.7 min) were much lower than for HT (9.5 min, p0.01) and IMRT (9.2 min, p0.01).Our results indicate that VMAT provides better sparing of normal tissue, homogeneity, and conformity than IMRT, and shorter delivery time than HT.

On-line cone-beam computed tomography (CBCT) may be used to reconstruct the dose for geometric changes of patients and tumors during radiotherapy course. This study is to establish a practical method to modify the CBCT for accurate dose calculation in head and neck cancer.Fan-beam CT (FBCT) and Elekta's CBCT were used to acquire images. The CT numbers for different materials on CBCT were mathematically modified to match them with FBCT. Three phantoms were scanned by FBCT and CBCT for image uniformity, spatial resolution, and CT numbers, and to compare the dose distribution from orthogonal beams. A Rando phantom was scanned and planned with intensity-modulated radiation therapy (IMRT). Finally, two nasopharyngeal cancer patients treated with IMRT had their CBCT image sets calculated for dose comparison.With 360° acquisition of CBCT and high-resolution reconstruction, the uniformity of CT number distribution was improved and the otherwise large variations for background and high-density materials were reduced significantly. The dose difference between FBCT and CBCT was2% in phantoms. In the Rando phantom and the patients, the dose-volume histograms were similar. The corresponding isodose curves covering ≥ 90% of prescribed dose on FBCT and CBCT were close to each other (within 2 mm). Most dosimetric differences were from the setup errors related to the interval changes in body shape and tumor response.The specific CBCT acquisition, reconstruction, and CT number modification can generate accurate dose calculation for the potential use in adaptive radiotherapy.

To assess bladder filling status and its impact on target position during daily intensity-modulated radiation therapy (IMRT) using cone-beam computed tomography (CBCT) in prostate cancer patients.23 patients with prostate cancer undergoing image-guided IMRT (78 Gy in 39 fractions) were included. On-board CBCT images were acquired daily and an endorectal balloon was placed daily. All patients were instructed to have a full bladder. The interfraction changes in bladder dimensions in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured from CBCT images. Distances from the uppermost part of prostate to pubic bone (PP) and from the uppermost part of prostate to treatment isocenter (PI) were measured to determine changes in target position. Standard deviation (SD) in all fractions of each patient was used to compare the variations between patients. Bladder dimension change ratio and Z-score were used to normalize data between patients.A total of 867 CBCT images were evaluated. The average LR, AP, and SI bladder dimensions were 7.8 +/- 1.5 cm, 6.7 +/- 1.4 cm, and 5.6 +/- 1.7 cm, respectively. The average LR, AP, and SI bladder dimension change ratios were 0.88 +/- 0.17, 0.90 +/- 0.15, and 0.86 +/- 0.32, respectively. The SD was significantly greater in SI dimension than in LR (p0.001) and AP (p0.001) dimensions. The interfraction changes in the three bladder dimensions were significantly larger than those of target position, and did not correlate with target position changes.Though they were not negligible, changes in bladder filling status did not have a significant impact on target position.

Purpose To investigate the set-up errors and deformation associated with daily placement of endorectal balloons in prostate radiotherapy. Materials and methods Endorectal balloons were placed daily in 20 prostate cancer patients undergoing radiotherapy. Electronic portal images (EPIs) were collected weekly from anterior–posterior (AP) and lateral views. The EPIs were compared with digitally reconstructed radiographs from computed tomography scans obtained during pretreatment period to estimate displacements. The interfraction deformation of balloon was estimated with variations in diameter in three orthogonal directions throughout the treatment course. Results A total of 154 EPIs were evaluated. The mean displacements of balloon relative to bony landmark were 1.8 mm in superior–inferior (SI), 1.3 mm in AP, and 0.1 mm in left–right (LR) directions. The systematic errors in SI, AP, and LR directions were 3.3 mm, 4.9 mm, and 4.0 mm, respectively. The random (interfraction) displacements, relative to either bony landmarks or treatment isocenter, were larger in SI direction (4.5 mm and 4.5 mm), than in AP (3.9 mm and 4.4 mm) and LR directions (3.0 mm and 3.0 mm). The random errors of treatment isocenter to bony landmark were 2.3 mm, 3.2 mm, and 2.6 mm in SI, AP, and LR directions, respectively. Over the treatment course, balloon deformations of 2.8 mm, 2.5 mm, and 2.6 mm occurred in SI, AP, and LR directions, respectively. The coefficient of variance of deformation was 7.9%, 4.9%, and 4.9% in these directions. Conclusions Larger interfractional displacement and the most prominent interfractional deformation of endorectal balloon were both in SI direction.

Purpose To investigate the correlation of the radiation dose to the upper rectum, proximal to the International Commission of Radiation Units and Measurements (ICRU) rectal point, with late rectal complications in patients treated with external beam radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary brachytherapy (ICRT) for carcinoma of the uterine cervix. Methods and materials Between June 1997 and February 2001, 75 patients with cervical carcinoma completed definitive or preoperative RT and were retrospectively reviewed. Of the 75 patients, 62 with complete dosimetric data and a minimal follow-up of at least 1 year were included in this analysis. Of the 62 patients, 36 (58%) also received concurrent chemotherapy, mainly with cisplatin during EBRT. EBRT consisted of a mean of 50.1 ± 1.3 Gy of 18-MV photons to the pelvis. A parametrial boost was given to 55 patients. Central shielding was used after 40–45 Gy of pelvic RT. HDR ICRT followed EBRT, with a median dose of 5 Gy/fraction given twice weekly for a median of four fractions. The mean dose to point A from HDR ICRT was 23.9 ± 3.0 Gy. In addition to the placement of a rectal tube with a lead wire during ICRT, 30–40 mL of contrast medium was instilled into the rectum to demonstrate the anterior rectal wall up to the rectosigmoid junction. Late rectal complications were recorded according to the Radiation Therapy Oncology Group grading system. The maximal rectal dose taken along the rectum from the anal verge to the rectosigmoid junction and the ICRU rectal dose were calculated. Statistical tests were used for the correlation of Grade 2 or greater rectal complications with patient-related variables and dosimetric factors. Correlations among the point A dose, ICRU rectal dose, and maximal proximal rectal dose were analyzed. Results Fourteen patients (23%) developed Grade 2 or greater rectal complications. Patient-related factors, definitive or preoperative RT, and the use of concurrent chemotherapy were not associated with the occurrence of rectal complications. The maximal rectal dose during ICRT was at the proximal rectum rather than at the ICRU rectal point in 55 (89%) of 62 patients. Patients with Grade 2 or greater rectal complications had received a significantly greater total maximal proximal rectal dose from ICRT (25.6 Gy vs. 19.2 Gy, p = 0.019) and had a greater maximal proximal rectal dose/point A dose ratio (1.025 vs. 0.813, p = 0.024). In contrast, patients with and without rectal complications had a similar dose at point A (25.0 Gy vs.23.6 Gy, p = 0.107). The differences in the ICRU rectal dose (17.8 Gy vs.15.4 Gy, p = 0.065) and the ICRU rectal dose/point A dose ratio (0.71 vs. 0.66, p = 0.210) did not reach statistical significance. Patients with >62 Gy of a direct dose sum from EBRT and ICRT to the proximal rectum (12 of 29 vs. 2 of 33, p = 0.001) and >110 Gy of a total maximal proximal rectal biologic effective dose (13 of 40 vs. 1 of 22, p = 0.012) presented with a significantly increased frequency of Grade 2 or greater rectal complications. The correlations between the maximal proximal rectal dose and the ICRU rectal dose were less satisfactory (Pearson coefficient 0.375). Moreover, 11 of the 14 patients with rectal complications had colonoscopic findings of radiation colitis at the proximal rectum, the area with the maximal rectal dose. Conclusion Eighty-nine percent of our patients had a maximal rectal dose from ICRT at the proximal rectum instead of the ICRU rectal point. The difference between patients with and without late rectal complications was more prominent for the proximal rectal dose than for the ICRU rectal dose. It is important and useful to contrast the whole rectal wall up to the rectosigmoid junction and to calculate the dose at the proximal rectum for patients undergoing HDR ICRT.

This study compares the difference in dose-volume data between three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for patients with hepatocellular carcinoma (HCC) and previously documented radiation-induced liver disease (RILD) after 3D-CRT.Between November 1993 and December 1999, 68 patients with HCC were treated with 3D-CRT at our institution. Twelve of them were diagnosed with RILD within 4 months of completion of 3D-CRT. RILD was defined as either anicteric elevation of alkaline phosphatase level of at least twofold and nonmalignant ascites, or elevated transaminases of at least fivefold the upper limit of normal or of pretreatment levels. Three-dimensional treatment planning using dose-volume histograms of normal liver was used to obtain the dose-volume data. These 12 patients with RILD were replanned with an IMRT planning system using the five-field (gantry angles 0 degrees, 72 degrees, 144 degrees, 216 degrees, and 288 degrees ) step-and-shoot technique to compare the dosimetric difference in targets and organs at risk between 3D-CRT and IMRT. Mean dose and normal tissue complication probability with literature-cited volume effect parameter of 0.32, curve steepness parameter of 0.15, and TD(50)(1) of 40 Gy, were used for the liver, whereas volume fraction at a given dose level was used for other critical structures. Paired Student t-test with 2-tailed p0.05 was used to assess the statistical difference between the two techniques.With comparable target coverage between 3D-CRT and five-field step-and-shoot IMRT, IMRT was able to obtain a large dose reduction in the spinal cord (5.7% vs. 33.2%, p = 0.007), and achieved at least similar organ sparing for kidneys and stomach. IMRT had diverse dosimetric effect on liver, with significant reduction in normal tissue complication probability (23.7% vs. 36.6%, p = 0.009), but significant increase in mean dose (2924 cGy vs. 2504 cGy, p = 0.009), as compared with 3D-CRT.IMRT is capable of preserving acceptable target coverage and improving or at least maintaining the nonhepatic organ sparing for patients with HCC and previously diagnosed RILD after 3D-CRT. The true impact of this technique on the liver remains unsettled and may depend on the exact volume effect of this organ.

Purpose: To analyze the correlation of radiation-induced liver disease (RILD) with patient-related and treatment-related dose-volume factors and to describe the probability of RILD by a normal tissue complication probability (NTCP) model for patients with hepatocellular carcinoma (HCC) treated with three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: Between November 1993 and December 1999, 93 patients with intrahepatic malignancies were treated with 3D-CRT at our institution. Sixty-eight patients who were diagnosed with HCC and had complete 3D dose-volume data were included in this study. Of the 68 patients, 50 had chronic viral hepatitis before treatment, either type B or type C. According to the Child-Pugh classification for liver cirrhosis, 53 patients were in class A and 15 in class B. Fifty-two patients underwent transcatheter arterial chemoembolization with an interval of at least 1 month between transcatheter arterial chemoembolization and 3D-CRT to allow adequate recovery of hepatic function. The mean dose of radiation to the isocenter was 50.2 ± 5.9 Gy, in daily fractions of 1.8–2Gy. No patient received whole liver irradiation. RILD was defined as Grade 3 or 4 hepatic toxicity according to the Common Toxicity Criteria of the National Cancer Institute. All patients were evaluated for RILD within 4 months of RT completion. Three-dimensional treatment planning with dose-volume histogram analysis of the normal liver was used to compare the dosimetric difference between patients with and without RILD. Maximal likelihood analysis was conducted to obtain the best estimates of parameters of the Lyman NTCP model. Confidence intervals of the fitted parameters were estimated by the profile likelihood method. Results: Twelve of the 68 patients developed RILD after 3D-CRT. None of the patient-related variables were significantly associated with RILD. No difference was found in tumor volume (780 cm 3 vs. 737 cm 3 , p = 0.86), normal liver volume (1210 cm 3 vs. 1153 cm 3 , p = 0.64), percentage of normal liver volume with radiation dose >30 Gy (V 30 Gy ; 42% vs. 33%, p = 0.05), and percentage of normal liver volume with >50% of the isocenter dose (V 50% ; 45% vs. 36%, p = 0.06) between patients with and without RILD. The mean hepatic dose was significantly higher in patients with RILD (2504 cGy vs. 1965 cGy, p = 0.02). The probability of RILD in patients could be expressed as follows: probability=1/[1 + exp −(0.12 × mean dose − 4.29) ], with coefficients significantly different from 0. The best estimates of the parameters in the Lyman NTCP model were the volume effect parameter of 0.40, curve steepness parameter of 0.26, and 50% tolerance dose for uniform irradiation of whole liver [TD 50 (1)] of 43 Gy. Patients with RILD had a significantly higher NTCP than did those with no RILD (26.2% vs. 15.8%; p = 0.006), using the best-estimated parameters. Conclusion: Dose-volume histogram analysis can be effectively used to quantify the tolerance of the liver to RT. Patients with RILD had received a significantly higher mean dose to the liver and a significantly higher NTCP. The fitted volume effect parameter of the Lyman NTCP model was close to that from the literature, but much lower in our patients with HCC and prevalent chronic viral hepatitis than that reported in other series with patients with normal liver function. Additional efforts should be made to test other models to describe the radiation tolerance of the liver for Asian patients with HCC and preexisting compromised hepatic reserve.

Twelve patients with hepatocellular carcinoma and chronic hepatitis developed radiation-induced liver disease (RILD) after three-dimensional conformal radiotherapy. Six patients died of RILD and six recovered. Mean prescribed dose was 50.6+/-4.3Gy, in a daily fraction of 1.8-2.0Gy. Commonly used dosimetric parameters, such as fraction volume of normal liver with radiation dose >30Gy, prediction score, and normal tissue complication probability, failed to differentiate the fatality and clinical types of this complication. Elevated transaminases are more frequently seen than ascites and elevated alkaline phosphamide are seen in patients with RILD.

Purpose/Objective(s): The accurate volumetric estimation of structures during organ motion forms the prerequisite basis of using cone-beam computed tomography (CBCT) images for future re-planning purposes. This study aimed to solve the problem of reconstructed volume loss of moving phantoms on CBCT by phase selected 4dimensional image acquisition. Materials/Methods: Phantom images were separately acquired by fan-beam CT (Siemens Somatom) and CBCT using X-ray Volumetric Image System on Elekta Synergy. Three acrylic ball phantoms with diameters of 5.1 cm, 9.9 cm, and 12.2 cm, respectively, were used for static and moving experiments. CBCT and FBCT images were imported to Pinnacle treatment planning system to compare the reconstructed volumes. The imaging adjustment program of CBCT was done for modified CBCT (mCBCT) by MATLAB v7.0 to modify CT numbers by transforming the functions to relative electron density for the more accurate calculation. The phantoms on FBCT and CBCT images were contoured with the CT number of 800. To simulate respiratory movement, the phantoms were moved longitudinally on an oscillator with amplitudes of 7.5, 10, 12.5, 15, 17.5 and 20 mm, and frequencies of 8, 10, 12, 14, 16 and 20 oscillations per minute, respectively. The imaging projections of mCBCT for moving phantoms selected from the same phases were used for 4-dimensional volume reconstruction (mSortCBCT). Results: For static phantoms with imaging adjustment program, the losses in reconstructed volume of 3 phantoms (small, medium, large) between FBCT and mCBCT were 6.20%, 2.47%, and 2.19%, respectively. For moving phantoms, the significant reconstructed volume losses of 3 phantoms seen on mCBCT were 47.45-66.04%, 23.8633.26%, and 15.53-22.65%, respectively. The volume losses significantly increased with the larger amplitude. In contrast, the volume losses did not differ between different frequencies. More volume losses in the small than large phantoms were again shown. The losses in reconstructed volume of moving phantoms between FBCT and mSortCBCT were significantly reduced, with 4.43% using the amplitude of 7.5mm and frequency of 20 per minute. Conclusions: As compared to the static targets, significant volume loss was seen on mCBCT for the moving phantom. The increased amplitude, but not frequency, correlated with more volume losses. mSortCBCT using 4dimensional phase selected projections for reconstruction reduced the volume losses for the moving phantoms.

Purpose: To determine the optimal parameters in the acquisition of cone‐beam computed tomography(CBCT) for good image quality and to modify the CT numbers for accurate dose calculation in head and neck cancer.Method and Materials: Systems of fan‐beam CT (FBCT) and CBCT were used to acquire images. A program was developed to establish the averaged CT numbers for different materials, and plot them as a function of density. CT numbers of CBCT were modified to match those of FBCT. The modified CBCTimages were used for dose calculation. Three CT phantoms were scanned by FBCT and CBCT for image uniformity, spatial resolution,CT numbers, and for comparing doses from orthogonal beams. A Rando phantom was scanned for head and neck regions by both FBCT and CBCT, and planned with intensity modulated radiation therapy(IMRT). In addition, the CBCTimages at the first and sixth weeks of radiotherapy of a nasopharyngeal cancer patient treated with an IMRT plan were calculated for dose comparison. Results: With 360°acquisition of CBCTimages, and high‐resolution reconstruction, the uniformity of CT number distribution was improved and the otherwise large variations of CT numbers for background and high‐density materials were reduced significantly. The dose difference between FBCT and CBCT was

Volumetric modulated arc therapy (VMAT) has been developed for the better dose conformity and shorter treatment time. This study is aimed to compare the dosimetric and treatment parameters between step‐and‐shoot intensity modulated radiation therapy(IMRT), helical tomotherapy (HT), and volumetric modulated arc therapy (VMAT). Eight patients with localized prostate cancer with the dosimetric plans of 5‐field IMRT, HT, and VMAT for their 78‐Gy definitive treatment formed the basis of the study. Treatment target was prostate and proximal seminal vesicles. The goals were minimum clinical target volume (CTV) dose ≥ 78Gy, and 95% of planning target volume (PTV) ≥ 78Gy in 39 fractions. Target comparison showed PTV V95% of 99.95±0.05% for VMAT, 99.84±0.21% for IMRT, and 99.39±0.49% for HT; maximum dose to PTV was 82.44±0.29Gy, 82.45±0.54Gy, 82.80±0.72Gy, respectively. The rectum V65Gy was 11.18±1.52% for VMAT, 13.77±1.68% for IMRT, and 8.44±1.13% for HT, respectively. The bladder V65Gy was 13.25±8.22% for VMAT, 16.51±11.05 % for IMRT, and 10.63±4.47% for HT, respectively. Total monitor units were 304.3±42.3 for VMAT, 335.8±19.0 for IMRT, and 3073.4±532.6 for HT, respectively. Treatment time was 2.47±0.10 minutes for VMAT, 3.71±0.29 minutes for IMRT, and 3.64±0.60 minutes for HT, respectively. The VMAT plans in all 8 patients met the quality assurance criteria of 3% and 3mm. In conclusion, VMAT is a practical technique with comparable target coverage, better organ sparing than IMRT, and superior treatment efficiency to HT in prostate cancer patients.

Hybrid positron emission tomography-computed tomography (PET-CT) system enhances better differentiation of tissue uptake of 18F-fluorodeoxyglucose (18F-FDG) and provides much more diagnostic value in the non-small-cell lung cancer and nasopharyngeal carcinoma (NPC). In PET-CT, high quality CT images not only offer diagnostic value on anatomic delineation of the tissues but also shorten the acquisition time for attenuation correction (AC) compared with PET-alone imaging. The linear accelerators equipped with the X-ray cone-beam computed tomography (CBCT) imaging system for image-guided radiotherapy (IGRT) provides excellent verification on position setup error. The purposes of our study were to optimize the CT acquisition protocols of PET-CT and to integrate the PET-CT and CBCT for IGRT. The CT imaging parameters were modified in PET-CT for increasing the image quality in order to enhance the diagnostic value on tumour delineation. Reproducibility and registration accuracy via bone co-registration algorithm between the PET-CT and CBCT were evaluated by using a head phantom to simulate a head and neck treatment condition. Dose measurement in computed tomography dose index (CTDI) was also estimated. Optimization of the CT acquisition protocols of PET-CT was feasible in this study. Co-registration accuracy between CBCT and PET-CT on axial and helical modes was in the range of 1.06 to 2.08 and 0.99 to 2.05 mm, respectively. In our result, it revealed that the accuracy of the co-registration with CBCT on helical mode was more accurate than that on axial mode. Radiation doses in CTDI were 4.76 to 18.5 mGy and 4.83 to 18.79 mGy on axial and helical modes, respectively. Registration between PET-CT and CBCT is a state-of-the-art registration technology which could provide much information on diagnosis and accurate tumour contouring on radiotherapy while implementing radiotherapy procedures. This novelty technology of PET-CT and cone-beam CT integration for IGRT may have a potential becoming more clinical use in the future.

Purpose: This study is to analyze the difference in reconstructing volume by using phantom model between various settings of axial‐mode and spiral‐mode computed tomography(CT) simulator for three dimensional conformal radiotherapy.Method and Materials: Three phantom balls with different diameters (5.1, 9.9, 12.2 cm) were scanned by a single‐row detector CT simulator. The volumes of all phantom balls were reconstructed in the same system. The exactly calculated phantom ball volumes were the baselines as compared to the volumes by the conventional axial CT reconstruction. The reconstructed volumes from the axial‐scanning‐mode were compared with the corresponding settings of the spiral‐scanning‐mode in CT simulation, with four different Hounsfield thresholds, three different pitches (1, 1.5 and 2), and four different slice intervals (1, 2, 3 and 5 mm). Results: The larger slice width and HU threshold were associated with larger difference between the exactly calculated volumes and reconstructed volumes in axial CT mode. The volume losses were more than 5% for small phantom ball in all axial CT settings. The lowest HU threshold and slice width of less than 5 mm were needed to maintain the volume loss of less than 5% in medium and large balls. As compared to axial scanning, spiral scanning offered the volume reconstruction loss of less than 5% in almost all settings. The exceptions existed in the small phantom ball with the slice interval of 5 mm, spiral pitch of 1.5 and 2 at 50 HU, and slice interval of 5 mm, spiral pitch of 2 at 0 HU. Conclusion: Slice interval, spiral scanning pitch and HU threshold were the factors with the impact on the accurate estimation of volume reconstruction by spiral CT simulator. Spiral CT mode was feasible in most scanning settings with the acceptable volume reconstruction accuracy threshold of more than 95%.

Materials/Methods: From 1993 to 2001 a total of 151 patients (89 with hepatocellular carcinoma and 62 with gastric cancer) underwent 3DCRT to part of liver were included in this study. The isocenter dose ranged from 33.0 to 66.0Gy (mean: 48.0Gy). Dose distribution and the corresponding volumetric data were obtained from the computerized planning system. A complication (RILD) was defined as grade 3 or higher RTOG liver toxicity within 4 months after completing 3DCRT. Patient-related and dosimetric factors were tested for their correlation with RILD in univariate and multivariate analyses. A maximal likelihood analysis was used to yield the best estimates for the parallel NTCP model parameters of the whole group and the subgroups. Patients were divided by statistically significant non-dosimetric factors, which were integrated into the modeling process for better describing the occurrence of RILD. Goodness of fit analysis was used to estimate the deviance of NTCP model parameters of subgroups from the whole group.