Impact of breath-hold level on positional error aligned by stent/Lipiodol in Hepatobiliary radiotherapy with breath-hold respiratory control.

BACKGROUND: Respiratory motion management with breath hold for patients with hepatobiliary cancers remain 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 < 1.4 L. Positional errors were similar for patients with ΔBHL< 0.03 L and > 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.

Developing a novel quasi-3D movable water phantom for radiation therapy workable in the magnetic resonance environment.

Background: The use of magnetic resonance linear accelerators (MR-LINACs) for clinical treatment has opened up new possibilities and challenges in the field of radiation oncology. However, annual quality assurance (QA) is relatively understudied due to practical considerations. Thus, to overcome the difficulty of measuring the dose with a small water phantom for TRS-398 or TG-51 in all external beam radiation treatment unit environments, such as MR compatibility, we designed a remote phantom with a three-axis changeable capacity for QA. Methods: The designed water phantom was tested under an MR environment. The water phantom system comprised of three parts: a phantom box, a dose measurement tool, and a PMD401 drive system. The UNIDOSE universal dosimeter was used to collect beam data. The manufacturer's developer tools were utilized to position the measurement. To ensure magnetic field homogeneity, a distortion phantom was prepared using sixty fish oil capsules aligned radially to distinguish the oil and free air. The phantom was scanned in both the MR simulator and computed tomography (CT), and the acquired images were analyzed to determine the position shift. Results: The dimensions of the device are 30 cm in the X-axis, 20 cm in the Y-axis, and 17 cm in the Z-axis. Total cost of materials was no more than $10,000 US dollars. Our results indicate that the device can function normally in a regular 1.5 T MR environment without interference from the magnetic field. The water phantom's traveling speed was found to be approximately 5 mm/s with a position difference confined within 6 cm intervals during normal use. The distortion test results showed that the prepared MR environment has uniform magnetic field homogeneity. Conclusions: In this study, we constructed a prototype water phantom device that can function in an MR simulator without interference between the magnetic field and electronic components. Compared to other commercially available MR-LINAC water phantoms, our device offers a more cost-effective solution for routine monthly QA. It can shorten the duration of QA tests and relieve the burden on medical physicists.

Low cost multifunctional 3D printed image quality and dose verification phantom for an image-guided radiotherapy system.

PURPOSE: Image-guided radiation therapy (IGRT) is used to precisely deliver radiation to a tumour to reduce the possible damage to the surrounding normal tissues. Clinics use various quality assurance (QA) equipment to ensure that the performance of the IGRT system meets the international standards set for the system. The objective of this study was to develop a low-cost and multipurpose module for evaluating image quality and dose. METHODS: A multipurpose phantom was designed to meet the clinical requirements of high accuracy, easy setup, and calibration. The outer shell of the phantom was fabricated using acrylic. Three dimensional (3D) printing technology was used to fabricate inner slabs with the characteristics of high spatial resolution, low-contrast detectability, a 3D grid, and liquid-filled uniformity. All materials were compatible with magnetic resonance (MR). Computed tomography (CT) simulator and linear accelerator (LINAC) modules were developed and validated. RESULTS: The uniformity slab filled with water is ideal for the assessment of Hounsfield units, whereas that filled with wax is suitable for consistency checks. The high-spatial-resolution slab enables measurements with a resolution up to 5 lp/cm. The low-contrast detectability slab contains rods of 5 different sizes that can be clearly visualised. These components meet the American College of Radiology (ACR) standards for QA of CT simulators and LINACs. CONCLUSIONS: The multifunctional phantom module meets the ACR recommended QA guidelines and is suitable for both LINACs and CT-sim. Further measurements in an MR simulator and an MR linear accelerator (MR-LINAC) will be arranged in the future.

Practically acquired and modified cone-beam computed tomography images for accurate dose calculation in head and neck cancer.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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 was < 2% 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. CONCLUSION: The specific CBCT acquisition, reconstruction, and CT number modification can generate accurate dose calculation for the potential use in adaptive radiotherapy.

Design of a motion simulation system to assist respiratory gating for radiation therapy.

Stereotactic ablative radiotherapy (SABR) aims to deliver high doses of radiation to kill cancer cells and shrink tumors in less than or equal to 6 fractions. However, organ motion during treatment is a challenging issue for this kind of technique. We develop a control system via Bluetooth technology to simulate and correct body motion during SABR. METHODS: Radiation doses were analyzed, and the radiation damage protection capability was checked by external beam therapy 3 (EBT3) films irradiated by a linear accelerator. A wireless signal test was also performed. A validation was performed with 8 previously treated patient respiratory pattern records and 8 healthy volunteers. RESULTS: The homemade simulation system consisted of 2 linear actuators, one movable stage with a maximal moving distance of 6.5 cm × 12.5 cm × 5 cm to simulate the respiratory pattern of 8 patients precisely with a median error of 0.36 mm and a maximal motion difference of 1.17 mm, and 3.17 and chipset transited signals to display them as a waveform. From the test with 8 volunteers, the chip could detect deep respiratory movement up to 3 cm. The effect of the chip on a radiation dose of 400 monitor units (MUs) by 6 MV photons and 200 MUs by 10 MV photons showed high penetration rates of 98.8% and 98.6%, respectively. CONCLUSIONS: We invented a tubeless and wireless respiratory gating detection chip. The chip has minimal interference with the treatment angles, good noise immunity and the capability to easily penetrate a variety of materials. The simulation system consisting of linear actuators also successfully simulates the respiratory pattern of real patients.

Association of clinical and dosimetric factors with postoperative pulmonary complications in esophageal cancer patients receiving intensity-modulated radiation therapy and concurrent chemotherapy followed by thoracic esophagectomy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Using cone-beam computed tomography to evaluate the impact of bladder filling status on target position in prostate radiotherapy.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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 (p < 0.001) and AP (p < 0.001) 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. CONCLUSION: Though they were not negligible, changes in bladder filling status did not have a significant impact on target position.

Set-up errors due to endorectal balloon positioning in intensity modulated radiation therapy for prostate cancer.

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 1.8mm in superior-inferior (SI), 1.3mm in AP, and 0.1mm in left-right (LR) directions. The systematic errors in SI, AP, and LR directions were 3.3mm, 4.9 mm, and 4.0mm, respectively. The random (interfraction) displacements, relative to either bony landmarks or treatment isocenter, were larger in SI direction (4.5mm and 4.5mm), than in AP (3.9 mm and 4.4mm) and LR directions (3.0mm and 3.0mm). The random errors of treatment isocenter to bony landmark were 2.3mm, 3.2mm, and 2.6mm in SI, AP, and LR directions, respectively. Over the treatment course, balloon deformations of 2.8mm, 2.5mm, and 2.6mm 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.

Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation.

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.

Inclusion of biological factors in parallel-architecture normal-tissue complication probability model for radiation-induced liver disease.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: RILD developed in 25 patients. Hepatitis B virus carrier status (p < 0.001) 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. CONCLUSIONS: 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.

Unique role of proximal rectal dose in late rectal complications for patients with cervical cancer undergoing high-dose-rate intracavitary brachytherapy.

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.

Dosimetric analysis and comparison of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy for patients with hepatocellular carcinoma and radiation-induced liver disease.

PURPOSE: 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. MATERIALS AND METHODS: 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 p < 0.05 was used to assess the statistical difference between the two techniques. RESULTS: 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. CONCLUSIONS: 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.

Biologic susceptibility of hepatocellular carcinoma patients treated with radiotherapy to radiation-induced liver disease.

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.

Radiation-induced liver disease after three-dimensional conformal radiotherapy for patients with hepatocellular carcinoma: dosimetric analysis and implication.

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 x 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.

Radiation-induced liver disease after radiotherapy for hepatocellular carcinoma: clinical manifestation and dosimetric description.

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.

Lumbosacral spine and marrow cavity modeling of acute hematologic toxicity in patients treated with intensity modulated radiation therapy for squamous cell carcinoma of the anal canal.

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 TD50 = 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.

Early detection of Lewis lung carcinoma tumor control by irradiation using diffusion-weighted and dynamic contrast-enhanced MRI.

PURPOSE: To investigate the correlation between diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) derived parameters and radioresponsiveness of Lewis lung carcinoma (LLC) tumor. MATERIALS AND METHODS: LLC tumor growth in C57BL/6 mouse limb was used for the experiment. The tumors were irradiated with 10 Gy×5, or 30 Gy×2 vs. sham irradiation. Fourteen tumors were subjected to DW-MRI and DCE-MRI pre-radiotherapy and weekly imaging after radiotherapy. The temporal changes in apparent diffusion coefficient (ADC) and DCE-MRI derived parameters (K(trans), k(ep), v(e), and v(p)) were correlated with tumor size, and were histologically compared with CD31 staining of resected tumors. RESULTS: The 10 Gy×5 dose inhibited tumor growth for a week, while 30 Gy×2 controlled tumor growth for a 3-week observation period. One week after radiotherapy (week 2), irradiated tumors showed significantly higher values of ADC than untreated ones (10 Gy×5, p = 0.004; 30 Gy×2, p = 0.01). Significantly higher values of v(e) were shown earlier by 30 Gy×2 vs. sham (p = 0.01) and 10 Gy×5 vs. sham irradiation (p = 0.05). Sustained higher v(e) from 10 Gy×5 compared to sham irradiated tumors was evident at week 3 (p = 0.016) and week 4 (p = 0.046). A 13.8% early increase in ADC for 30 Gy×2 tumor group (p = 0.002) and a 16.5% increase for 10 Gy×5 group were noted (p = 0.01) vs. sham irradiation (which showed a 2.2% decrease). No differences were found for K(trans), k(ep), or v(p). Both radiotherapy groups demonstrated significant reduction in microvessel counts. CONCLUSION: Early increase in ADC and v(e) correlated with tumor control by irradiation.

Programmable segmented volumetric modulated arc therapy for respiratory coordination in pancreatic cancer.

We programmably divided long-arc volumetric modulated arc therapy (VMAT) into split short arcs, each taking less than 30s 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.

Volumetric modulated arc therapy for nasopharyngeal carcinoma: a dosimetric comparison with TomoTherapy and step-and-shoot IMRT.

PURPOSE: 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. MATERIALS AND METHODS: 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). RESULTS: 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, p<0.05). 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 (p<0.05). 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, p<0.01). The delivery time per fraction for VMAT (5.7 min) were much lower than for HT (9.5 min, p<0.01) and IMRT (9.2 min, p<0.01). CONCLUSIONS: Our results indicate that VMAT provides better sparing of normal tissue, homogeneity, and conformity than IMRT, and shorter delivery time than HT.

Treatment and dosimetric advantages between VMAT, IMRT, and helical tomotherapy in prostate cancer.

We investigated the possible treatment and dosimetric advantage of volumetric modulated arc therapy (VMAT) over step-and-shoot intensity-modulated radiation therapy (step-and-hhoot IMRT) and helical tomotherapy (HT). Twelve prostate cancer patients undergoing VMAT to the prostate were included. Three treatment plans (VMAT, step-and-shoot IMRT, HT) were generated for each patient. The doses to clinical target volume and 95% of planning target volume were both ≥ 78 Gy. Target coverage, conformity index, dose to rectum/bladder, monitor units (MU), treatment time, equivalent uniform dose (EUD), normal tissue complication probability (NTCP) of targets, and rectum/bladder were compared between techniques. HT provided superior conformity and significantly less rectal volume exposed to 65 Gy and 40 Gy, as well as EUD/NTCP of rectum than step-and-shoot IMRT, whereas VMAT had a slight dosimetric advantage over step-and-shoot IMRT. Notably, significantly lower MUs were needed for VMAT (309.7 ± 35.4) and step-and-shoot IMRT (336.1 ± 16.8) than for HT (3368 ± 638.7) (p < 0.001). The treatment time (minutes) was significantly shorter for VMAT (2.6 ± 0.5) than step-and-shoot IMRT (3.8 ± 0.3) and HT (3.8 ± 0.6) (p < 0.001). Dose verification of VMAT using point dose and film dosimetry met the accepted criteria. VMAT and step-and-shoot IMRT have comparable dosimetry, but treatment efficiency is significantly higher for VMAT than for step-and-shoot IMRT and HT.