Does the evidence support the enthusiasm over 3D conformal radiation therapy and dose escalation in the treatment of prostate cancer?
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Attitude of Health Personnel↗
Biomedical subjects
J A Purdy
Publications and source records attributed to J A Purdy.
Multimodality image registration quality assurance for conformal three-dimensional treatment planning.
PURPOSE: We present a quality assurance methodology to determine the accuracy of multimodality image registration and fusion for the purpose of conformal three-dimensional and intensity-modulated radiation therapy treatment planning. Registration and fusion accuracy between any combination of computed tomography (CT), magnetic resonance (MR), and positron emission computed tomography (PET) imaging studies can be evaluated. METHODS AND MATERIALS: A commercial anthropomorphic head phantom filled with water and containing CT, MR, and PET visible targets was modified to evaluate the accuracy of multimodality image registration and fusion software. For MR and PET imaging, the water inside the phantom was doped with CuNO(3) and 18F-fluorodeoxyglucose (18F-FDG), respectively. Targets consisting of plastic spheres and pins were distributed throughout the cranium section of the phantom. Each target sphere had a conical-shaped bore with its apex at the center of the sphere. The pins had a conical extension or indentation at the free end. The contours of the spheres, sphere centers, and pin tips were used as anatomic landmark models for image registration, which was performed using affine coordinate-transformation tools provided in a commercial multimodality image registration/fusion software package. Four sets of phantom image studies were obtained: primary CT, secondary CT with different phantom immobilization, MR, and PET study. A novel CT, MR, and PET external fiducial marking system was also tested. RESULTS: The registration of CT/CT, CT/MR, and CT/PET images allowed correlation of anatomic landmarks to within 2 mm, verifying the accuracy of the registration software and spatial fidelity of the four multimodality image sets. CONCLUSIONS: This straightforward phantom-based quality assurance of the image registration and fusion process can be used in a routine clinical setting or for providing a working image set for development of the image registration and fusion process and new software.
Head and Neck Neoplasms↗
Room shielding for intensity-modulated radiation therapy treatment facilities.
PURPOSE: The traditional assumptions used in room-shielding calculations are reassessed for intensity-modulated radiation therapy (IMRT). IMRT makes relatively inefficient use of monitor units (MUs) when compared to conventional radiation therapy, affecting the assumptions used in room-shielding calculations. For the same single-fraction tumor dose delivered, the total number of MUs for IMRT is much greater than for a conventional treatment. Therefore, the exposure contribution from the linear accelerator head leakage will be significantly greater than with conventional treatments. METHODS AND MATERIALS: We propose a shielding calculation model that decouples the concepts of workload, MUs, and target dose when determining primary and secondary barrier thicknesses. The workload for primary barrier calculations for conventional multileaf collimator (MLC) IMRT treatments is determined according to patient tumor doses. The same calculation for accelerator-based serial tomotherapy IMRT requires scaling by the average number of treatment slices. However, rotational therapy yields a small use factor that compensates for this increase. We further define a series of efficiency factors to account for the small field sizes employed in IMRT. For secondary barrier calculations, the patient-scattered radiation is assumed to be the same for all IMRT modalities as for conventional therapy. The accelerator head leakage contribution is proportional to the number of MUs. Knowledge of the average number of MUs per patient is required to estimate the head leakage contribution. We used a 6-MV linear accelerator photon beam to guide the development of this technique and to evaluate the adequacy of conventional barriers for IMRT. Average weekly IMRT workload estimates were made based on our experience with 180 serial tomotherapy patients and published data for both "step and shoot" and dynamic MLC delivered treatments. RESULTS: We found that conventional primary barriers are adequate for both dynamic MLC and serial tomotherapy IMRT. However, the excessive head leakage produced by these modalities requires an increase in secondary barrier shielding. CONCLUSION: When designing shielding for an IMRT facility, increases in accelerator head leakage must be taken into account for secondary shielding. Adequacy of secondary shielding will depend on the IMRT patient load. For conventional facilities that are being assessed for IMRT therapy, existing primary barriers will typically prove adequate.
Facility Design and Construction↗
A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy.
PURPOSE: Locoregional tumor control for locally advanced cancers with radiation therapy has been unsatisfactory. This is in part associated with the phenomenon of tumor hypoxia. Assessing hypoxia in human tumors has been difficult due to the lack of clinically noninvasive and reproducible methods. A recently developed positron emission tomography (PET) imaging-based hypoxia measurement technique which employs a Cu(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-ATSM) tracer is of great interest. Oxygen electrode measurements in animal experiments have demonstrated a strong correlation between low tumor pO(2) and excess (60)Cu-ATSM accumulation. Intensity-modulated radiation therapy (IMRT) allows selective targeting of tumor and sparing of normal tissues. In this study, we examined the feasibility of combining these novel technologies to develop hypoxia imaging (Cu-ATSM)-guided IMRT, which may potentially deliver higher dose of radiation to the hypoxic tumor subvolume to overcome inherent hypoxia-induced radioresistance without compromising normal tissue sparing. METHODS AND MATERIALS: A custom-designed anthropomorphic head phantom containing computed tomography (CT) and positron emitting tomography (PET) visible targets consisting of plastic balls and rods distributed throughout the "cranium" was fabricated to assess the spatial accuracy of target volume mapping after multimodality image coregistration. For head-and-neck cancer patients, a CT and PET imaging fiducial marker coregistration system was integrated into the thermoplastic immobilization head mask with four CT and PET compatible markers to assist image fusion on a Voxel-Q treatment-planning computer. This system was implemented on head-and-neck cancer patients, and the gross tumor volume (GTV) was delineated based on physical and radiologic findings. Within GTV, regions with a (60)Cu-ATSM uptake twice that of contralateral normal neck muscle were operationally designated as ATSM-avid or hypoxic tumor volume (hGTV) for this feasibility study. These target volumes along with other normal organs contours were defined and transferred to an inverse planning computer (Corvus, NOMOS) to create a hypoxia imaging-guided IMRT treatment plan. RESULTS: A study of the accuracy of target volume mapping showed that the spatial fidelity and imaging distortion after CT and PET image coregistration and fusion were within 2 mm in phantom study. Using fiducial markers to assist CT/PET imaging fusion in patients with carcinoma of the head-and-neck area, a heterogeneous distribution of (60)Cu-ATSM within the GTV illustrated the success of (60)Cu-ATSM PET to select an ATSM-avid or hypoxic tumor subvolume (hGTV). We further demonstrated the feasibility of Cu-ATSM-guided IMRT by showing an example in which radiation dose to the hGTV could be escalated without compromising normal tissue (parotid glands and spinal cord) sparing. The plan delivers 80 Gy in 35 fractions to the ATSM-avid tumor subvolume and the GTV simultaneously receives 70 Gy in 35 fractions while more than one-half of the parotid glands are spared to less than 30 Gy. CONCLUSION: We demonstrated the feasibility of a novel Cu-ATSM-guided IMRT approach through coregistering hypoxia (60)Cu-ATSM PET to the corresponding CT images for IMRT planning. Future investigation is needed to establish a clinical-pathologic correlation between (60)Cu-ATSM retention and radiation curability, to understand tumor re-oxygenation kinetics, and tumor target uncertainty during a course of radiation therapy before implementing this therapeutic approach to patients with locally advanced tumor.
Algorithms↗
A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results.
OBJECTIVES: In a prospective clinical study, we tested the hypothesis that sparing the parotid glands may result in significant objective and subjective improvement of xerostomia in patients with head-and-neck cancers. The functional outcome 6 months after the completion of radiation therapy is presented. METHODS AND MATERIALS: From February 1997 to February 1999, 41 patients with head-and-neck cancers were enrolled in a prospective salivary function study. Inverse-planning intensity-modulated radiation therapy (IMRT) was used to treat 27 patients, and forward-planning three-dimensional radiation therapy in 14. To avoid potential bias in data interpretation, only patients whose submandibular glands received greater than 50 Gy were eligible. Attempts were made to spare the superficial lobe of the parotid glands to avoid underdosing tumor targets in the parapharyngeal space; however, the entire parotid volume was used to compute dose-volume histograms (DVHs) for this analysis. DVHs were computed for each gland separately. Parotid function was assessed objectively by measuring stimulated and unstimulated saliva flow before and 6 months after the completion of radiation therapy. Measurements were converted to flow rate (mL/min) and normalized relative to that before treatment. The corresponding quality-of-life (QOL) outcome was assessed by five questions regarding the patient's oral discomfort and eating/speaking problems. RESULTS: We observed a correlation between parotid mean dose and the fractional reduction of stimulated saliva output at 6 months after the completion of radiation therapy. We further examined whether the functional outcome could be modeled as a function of dose. Two models were found to describe the dose-response data well. The first model assumed that each parotid gland is comprised of multiple independent parallel functional subunits (corresponding to computed tomography voxels) and that each gland contributes equally to overall flow, and that saliva output decreases exponentially as a quadratic function of irradiation dose to each voxel. The second approach uses the equivalent uniform dose (EUD) metrics, which assumes loss of salivary function with increase in EUD for each parotid gland independently. The analysis suggested that the mean dose to each parotid gland is a reasonable indicator for the functional outcome of each gland. The corresponding exponential coefficient was 0.0428/Gy (95% confidence interval: 0.01, 0.09). The QOL questions on eating/speaking function were significantly correlated with stimulated and unstimulated saliva flow at 6 months. In a multivariate analysis, a toxicity score derived from the model based on radiation dose to the parotid gland was found to be the sole significant predictive factor for xerostomia. Neither radiation technique (IMRT vs. non-IMRT) nor chemotherapy (yes or no) independently influenced the functional outcome of the salivary glands. CONCLUSION: Sparing of the parotid glands translates into objective and subjective improvement of both xerostomia and QOL scores in patients with head-and-neck cancers receiving radiation therapy. Modeling results suggest an exponential relationship between saliva flow reduction and mean parotid dose for each gland. We found that the stimulated saliva flow at 6 months after treatment is reduced exponentially, for each gland independently, at a rate of approximately 4% per Gy of mean parotid dose.
Adult↗
Abutment dosimetry for serial tomotherapy.
The dose distributions at the abutment region for serial tomotherapy are reviewed. While tomotherapy provides unparalleled dose distributions, precise couch motion and good patient immobilization are required because the dose in the abutment region changes by 25% for each millimeter of misalignment. The process of delivering intensity-modulated radiation therapy using sequentially delivered modulated arcs yields hot spots below and cold spots above the machine isocenter when arc angles of less than 360 degrees are used. The magnitude of the hot and cold spots increases significantly as the arc angle is reduced 180 degrees such as when limited by couch clearance restrictions. Placement of isocenter also significantly affects the dose heterogeneity in the abutment region, with the hot and cold spots increasing nearly linearly with off-axis distance in the vertical direction. Reduction of the magnitude of the abutment region dose heterogeneities is possible if helical delivery is provided by moving the couch during arc delivery. The dose heterogeneity can also be reduced by creating 2 treatment plans, each with slightly different abutment region positions, or by using multiple couch angles.
Head and Neck Neoplasms↗
Angular measurement of the cobalt-60 emitted radiation spectrum from a radiosurgery irradiator.
The photon energy spectrum emanating from a Leksell Gamma Knife, Model 23004B, was measured between 0.250 and 3.5 MeV with the sources exposed. Measurements were made using a 2x2 inch NaI detector enclosed in a lead-shielded apparatus having a 1/4 inch diameter measurement aperture, which reduced the amount of radiation received by the crystal. All measurements were made one meter above the floor within a quadrant toward one side of the Gamma Knife couch. The measured spectra displayed the expected 60Co doublet of photon peaks at energies of 1.17 and 1.33 MeV. These peaks appeared in spectra beginning at approximately 50 degrees, as one proceeds from a point directly lateral to the source enclosure (0 degrees) toward the foot of the couch (90 degrees). The average photon energy of the spectrum shifts to lower values as the doublet decreases in magnitude with increasing angle until almost vanishing at an angle equal to 90 degrees. Inserting a 16 cm diameter plastic sphere phantom, provided with the Gamma Knife, into the radiation beams increases the low energy photon emissions appearing in the spectrum, especially for measurements at the foot of the couch. Implications for the design of shielding a treatment room containing the Gamma Knife, Model B, and estimation of the radiation exposure to personnel during an emergency procedure in the treatment room with the sources exposed are discussed.
Cobalt Radioisotopes↗
Radiation Therapy Oncology Group. Research Plan 2002-2006. Image-Guided Radiation Therapy Committee.
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Clinical Trials as Topic↗
Differential dosing of prostate and seminal vesicles using dynamic multileaf collimation.
PURPOSE: We have investigated the potential of applying different doses to the prostate (PTV2) and prostate/seminal vesicles (PTV1) using multileaf collimation (MLC) for intensity modulated radiation therapy (IMRT). Current dose-escalation studies call for treatment of the PTV1 to 54 Gy in 27 fractions followed by 20 Gy minimum to the PTV2. A daily minimum PTV dose of 2 Gy using a 7-field technique (4 obliques, opposed laterals, and an ant-post field) is delivered. This requires monitor unit calculations, paper and electronic chart entry, and quality assurance for a total of 14 fields. The goal of MLC IMRT is to improve efficiency and deliver superior dose distributions. Acceptance testing and commissioning of the dynamic MLC (DMLC) option on a dual-energy accelerator was accomplished. Most of the testing was performed using segmental MLC (SMLC) IMRT with stop-and-shoot sequences built within the dynamic mode of the DMLC. METHODS AND MATERIALS: The MLC IMRT fields were forward planned using a three-dimensional treatment planning system. The 14 fields were condensed to 7 SMLC IMRT fields with two segments each. In this process, steps were created by moving the leaves to the reduced field positions. No dose (<0.01%) was delivered during this motion. The monitor units were proportioned according to the planned treatment weights. Film and ionization chamber dosimetry were used to analyze leaf positional accuracy and speed, output, and depth-dose characteristics. A geometric phantom was used for absolute and relative measurements. We obtained a volumetric computerized tomography (CT) scan of the phantom, performed 3D planning, and then delivered a single treatment fraction. RESULTS: The acceptance testing and commissioning demonstrated that the leaves move to programmed positions accurately and in a timely manner. We did find an approximately 1 mm offset of the set leaf position and radiation edge (50%) due to the curved-end nature and calibration limitations. The 7-field SMLC IMRT treatment duplicated the 14-field static plan dose distribution with variations no greater than 1.5%. CONCLUSIONS: The MLC IMRT approach will improve efficiency because the number of electronic and chart entries has decreased by a factor of 2. Portal images are able to capture the initial and final MLC segments. The question of differential daily dose to the prostate and seminal vesicles remains.
Humans↗
Three-dimensional conformal therapy or standard irradiation in localized carcinoma of prostate: preliminary results of a nonrandomized comparison.
PURPOSE: We present preliminary results of a nonrandomized comparison of three-dimensional conformal radiation therapy (3D CRT) and standard radiation therapy (SRT) in localized carcinoma of the prostate in two groups of patients with comparable prognostic factors treated during the same period. METHODS AND MATERIALS: Between January 1992 and December 1997, 146 patients were treated with 3D CRT and 131 with SRT alone for clinical stage T1c or T2 histologically confirmed carcinoma of the prostate. None of these patients received hormonal therapy. Mean follow-up for all patients is 3 years (range, 1-6 years). For 3D CRT, 7 intersecting fields were used (Cerrobend blocking or multileaf collimation) to deliver 68-73.8 Gy to the prostate; 3D dose distributions and dose-volume histograms (DVHs) of the planning target volume, bladder, and rectum were obtained. SRT consisted of bilateral 120 degrees rotational arcs, with portals with 2-cm margins around the prostate to deliver 68-70 Gy to the prostate. The criterion for chemical disease-free survival was a postirradiation prostate-specific antigen (PSA) (Tandem-R, Hybritech) value following the American Society for Therapeutic Radiology and Oncology guidelines. Symptoms during treatment were quantitated weekly, and late effects were assessed every 4-6 months. RESULTS: DVHs showed a two-thirds reduction in normal bladder or rectum receiving 70 Gy or more with 3D CRT. Higher 5-year chemical disease-free survival was observed with 3D CRT (91% for T1c and 96% for T2 tumors) compared with SRT (53% and 58%, respectively). There was no statistically significant difference in chemical disease-free survival in patients with Gleason score of 4 or less (p = 0.83), but with Gleason score of 5-7, the 5-year survival rates were 96% with 3D CRT and 53% with SRT (p < or = 0.01). In 111 patients with pretreatment PSA of 10 ng/mL or less, treated with 3D CRT, the chemical disease-free rate was 96% vs. 65% in 94 patients treated with SRT (p < or = 0.01). In patients with PSA of 10. 1-20 ng/mL, the chemical disease-free survival rate for 26 patients treated with 3D CRT was 88% compared with 40% for 20 patients treated with SRT (p = 0.05). The corresponding values were 71% and 26%, respectively, for patients with PSA levels of greater than 20 ng/mL (p = 0.30). On multivariate analysis, the most important prognostic factors for chemical failure were pretreatment PSA (p = 0. 023), nadir PSA (p = 0.001), and 3D CRT technique (p = 0.033). Moderate dysuria and difficulty in urinating were reported by 2-5% of patients treated with 3D CRT in contrast to 6-9% of patients treated with SRT; moderate urinary frequency and nocturia were reported by 18-24% treated with 3D CRT and 18-27% of patients in the SRT group. The incidence of moderate loose stools/diarrhea, usually after the 4th week of treatment, was 3-5% in the 3D CRT patients and 8-19% in the SRT group. Late intestinal morbidity (proctitis, rectal bleeding) was very low (1.7%) in the 3D CRT group in contrast to the SRT patients (8%). CONCLUSION: Three-dimensional CRT spares more normal tissues, yields higher chemical disease-free survival, and results in less treatment morbidity than SRT in treatment of Stage T1-T2 prostate cancer. Longer follow-up is needed to confirm these preliminary observations.
Disease-Free Survival↗
Intensity-modulated radiation therapy in head and neck cancers: The Mallinckrodt experience.
The purpose of the study was to investigate the feasibility and the optimization of tomotherapy-based intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer. From February 1997 to November 1997, 17 patients with squamous cell carcinoma of the head and neck were treated with IMRT. Patients were immobilized with a noninvasive mask and treated using a serial tomotherapy device on a 6 MV linear accelerator. Treatment planning was performed on a Peacock inverse planning system and prescription optimization was used to achieve the best plan for target coverage and parotid sparing. The treatment planning system process has a dosimetric characteristic of delivering different doses to different target structures simultaneously in each daily treatment; therefore, the biological equivalent dose was implemented using the linear-quadratic model to adjust the total dose to the target volume receiving a daily dose of less than 1.9 Gy. All eight patients with gross disease (six in the nasopharynx, two in the tonsil) and one patient with recurrent nasopharyngeal carcinoma received concurrent cisplatin chemotherapy. Six postoperative patients were treated with irradiation alone. Median follow-up was 2.2 years (range 2.6-1.8 years). All patients completed the prescribed treatment without unexpected interruption. Acute side effects were comparable to those of patients treated with conventional beam arrangements during the same period. No patient required gastrostomy during irradiation. The preliminary experience showed that the noninvasive immobilization mask yielded high positioning reproducibility for our patients. To spare the parotid gland, which is in the proximity of the target, a fraction of the target volume may not receive the prescribed dose. In the best-achievable plan of our studied cohort, only 27% +/- 8% of parotid gland volumes were treated to more than 30 Gy, while an average of 3.3% +/- 0.6% of the target volume received less than 95% of the prescribed dose. This is mainly related to the steep dose gradient in the region where the target abuts the parotid gland. The inverse planning system allowed us the freedom of weighting normal tissue-sparing and target coverage to select the best-achievable plan. Local control was achieved in eight patients with gross tumor; six were treated postoperatively. Of three reirradiated patients, two had symptomatic improvement but persistent disease, and one is without evidence of disease. In summary, a system for patient immobilization, setup verification, and dose optimization for head and neck cancer with parotid sparing without significantly compromising target coverage is being implemented for a tomotherapy-based IMRT plan at the Mallinckrodt Institute of Radiology. The initial clinical experience in tumor control is promising, and no severe adverse acute side effects have been observed. Further refining of delivery technology and the inverse planning system, gaining clinical experience to address target definition and dose inhomogeneity within the targets, and understanding the partial volume effect on normal tissue tolerance are needed for IMRT to excel in the treatment of head and neck cancer. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 92-103, (2000).
Adult↗
Preliminary report of toxicity following 3D radiation therapy for prostate cancer on 3DOG/RTOG 9406.
PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally-tolerated radiation dose in men treated with three-dimensional conformal radiation therapy (3D CRT) for localized prostate cancer. This is a preliminary report of toxicity encountered on the 3DOG/RTOG 9406 study. METHODS AND MATERIALS: Each participating institution was required to implement data exchange with the RTOG 3D quality assurance (QA) center at Washington University in St. Louis. 3D CRT capabilities were strictly defined within the study protocol. Patients were registered according to three stratification groups: Group 1 patients had clinically organ-confined disease (T1,2) with a calculated risk of seminal vesicle invasion of < 15%. Group 2 patients had clinical T1,2 disease with risk of SV invasion > or = 15%. Group 3 (G3) patients had clinical local extension of tumor beyond the prostate capsule (T3). All patients were treated with 3D techniques with minimum doses prescribed to the planning target volume (PTV). The PTV margins were 5-10 mm around the prostate for patients in Group 1 and 5-10 mm around the prostate and SV for Group 2. After 55.8 Gy, the PTV was reduced in Group 2 patients to 5-10 mm around the prostate only. Minimum prescription dose began at 68.4 Gy (level I) and was escalated to 73.8 Gy (level II) and subsequently to 79.2 Gy (level III). This report describes the acute and late toxicity encountered in Group 1 and 2 patients treated to the first two study dose levels. Data from RTOG 7506 and 7706 allowed calculation of the expected probability of observing a > or = grade 3 late effect more than 120 days after the start of treatment. RTOG toxicity scores were used. RESULTS: Between August 23, 1994 and July 2, 1997, 304 Group 1 and 2 cases were registered; 288 cases were analyzable for toxicity. Acute toxicity was low, with 53-54% of Group 1 patients having either no or grade 1 toxicity at dose levels I and II, respectively. Sixty-two percent of Group 2 patients had either none or grade 1 toxicity at either dose level. Few patients (0-3%) experienced a grade 3 acute bowel or bladder toxicity, and there were no grade 4 or 5 toxicities. Late toxicity was very low in all patient groups. The majority (81-85%) had either no or mild grade 1 late toxicity at dose level I and II, respectively. A single late grade 3 bladder toxicity in a Group 2 patient treated to dose level II was recorded. There were no grade 4 or 5 late effects in any patient. Compared to historical RTOG controls (studies 7506, 7706) at dose level I, no grade 3 or greater late effects were observed in Group 1 and Group 2 patients when 9.1 and 4.8 events were expected (p = 0.003 and p = 0.028), respectively. At dose level II, there were no grade 3 or greater toxicities in Group 1 patients and a single grade 3 toxicity in a Group 2 patient when 12.1 and 13.0 were expected (p = 0.0005 and p = 0.0003), respectively. Multivariate analysis demonstrated that the relative risk of developing acute bladder toxicity was 2.13 if the percentage of the bladder receiving > or = 65 Gy was more than 30% (p = 0.013) and 2.01 if patients received neoadjuvant hormonal therapy (p = 0.018). The relative risk of developing late bladder complications also increased as the percentage of the bladder receiving > or = 65 Gy increased (p = 0.026). Unexpectedly, there was a lower risk of late bladder complications as the mean dose to the bladder and prescription dose level increased. This probably reflects improvement in conformal techniques as the study matured. There was a 2.1 relative risk of developing a late bowel complication if the total rectal volume on the planning CT scan exceeded 100 cc (p = 0.019). CONCLUSION: Tolerance to high-dose 3D CRT has been better than expected in this dose escalation trial for Stage T1,2 prostate cancer compared to low-dose RTOG historical experience. With strict quality assurance standards and review, 3D CRT can be safely studied in a co
Adult↗
Future directions in 3-D treatment planning and delivery: a physicist's perspective.
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Forecasting↗
Noise in polymer gel measurements using MRI.
With the development of conformal radiotherapy, particularly intensity modulated radiation therapy (IMRT), there is a clear need for multidimensional dosimeters. A commercial polymerizing gel, BANG-2 gel (MGS Research, Inc., Guilford, CT), has recently been developed that shows potential as a multi-dimensional dosimeter. This study investigates and characterizes the noise and magnetic resonance (MR) artifacts from imaging BANG-2 gels. Seven cylindrical vials (4 cm diam, 20 cm length) were irradiated end on in a water bath and read using MRI (B0=1.5 T, TE=20 ms/100 ms, TR=3000 ms). The gel calibration compared the measured depth-dose distributions in water against the change in solvent-proton R2 relaxivity of the gel. A larger vial (13 cm diam, 14 cm length) was also irradiated to test the calibration accuracy in a vial of sufficient volume for dose distribution measurements. The calibration curve proved accurate to within 1.3% in determining the depth dose measured by the larger vial. An investigation of the voxel-to-voxel (IXIX 3 mm3) noise and sensitivity response curve showed that the voxel-to-voxel variation dominated the dose measurement uncertainty. The voxel-to-voxel standard deviation ranged from 0.2 Gy for the unirradiated gel to 0.7 Gy at 20 Gy. Slice-to-slice R2 magnitude deviations were also observed corresponding to 0.2 Gy. These variations limited the overall accuracy of the gel dose measurements and warrant an investigation of more accurate MR readout sequences.
Calibration↗
Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC)
PURPOSE: To identify a clinically relevant and available parameter upon which to identify non-small cell lung cancer (NSCLC) patients at risk for pneumonitis when treated with three-dimensional (3D) radiation therapy. METHODS AND MATERIALS: Between January 1991 and October 1995, 99 patients were treated definitively for inoperable NSCLC. Patients were selected for good performance status (96%) and absence of weight loss (82%). All patients had full 3D treatment planning (including total lung dose-volume histograms [DVHs]) prior to treatment delivery. The total lung DVH parameters were compared with the incidence and grade of pneumonitis after treatment. RESULTS: Univariate analysis revealed the percent of the total lung volume exceeding 20 Gy (V20), the effective volume (Veff) and the total lung volume mean dose, and location of the tumor primary (upper versus lower lobes) to be statistically significant relative to the development of > or = Grade 2 pneumonitis. Multivariate analysis revealed the V20 to be the single independent predictor of pneumonitis. CONCLUSIONS: The V20 from the total lung DVH is a useful parameter easily obtained from most 3D treatment planning systems. The V20 may be useful in comparing competing treatment plans to evaluate the risk of pneumonitis for our individual patient treatment and may also be a useful parameter upon which to stratify patients or prospective dose escalation trials.
Adult↗
Abutment region dosimetry for serial tomotherapy.
PURPOSE: A commercial intensity modulated radiation therapy system (Corvus, NOMOS Corp.) is presently used in our clinic to generate optimized dose distributions delivered using a proprietary dynamic multileaf collimator (DMLC) (MIMiC) composed of 20 opposed leaf pairs. On our accelerator (Clinac 600C/D, Varian Associates, Inc.) each MIMiC leaf projects to either 1.00 x 0.84 or 1.00 x 1.70 cm2 (depending on the treatment plan and termed 1 cm or 2 cm mode, respectively). The MIMiC is used to deliver serial (axial) tomotherapy treatment plans, in which the beam is delivered to a nearly cylindrical volume as the DMLC is rotated about the patient. For longer targets, the patient is moved (indexed) between treatments a distance corresponding to the projected leaf width. The treatment relies on precise indexing and a method was developed to measure the precision of indexing devices. A treatment planning study of the dosimetric effects of incorrect patient indexing and concluded that a dose heterogeneity of 10% mm(-1) resulted. Because the results may be sensitive to the dose model accuracy, we conducted a measurement-based investigation of the consequences of incorrect indexing using our accelerator. Although the indexing provides an accurate field abutment along the isocenter, due to beam divergence, hot and cold spots will be produced below and above isocenter, respectively, when less than 300 degree arcs were used. A preliminary study recently determined that for a 290 degree rotation in 1 cm mode, 15% cold and 7% hot spots were delivered to 7 cm above and below isocenter, respectively. This study completes the earlier work by investigating the dose heterogeneity as a function of position relative to the axis of rotation, arc length, and leaf width. The influence of random daily patient positioning errors is also investigated. METHODS AND MATERIALS: Treatment plans were generated using 8.0 cm diameter cylindrical target volumes within a homogeneous rectilinear film phantom. The plans included both 1 and 2 cm mode, optimized for 300 degrees, 240 degrees, and 180 degrees gantry rotations. Coronal-oriented films were irradiated throughout the target volumes and scanned using a laser film digitizer. The central target irradiated in 1 cm mode was also used to investigate the effects of incorrect couch indexing. RESULTS: The dose error as a function of couch index error was 25% mm(-1), significantly greater than previously reported. The clinically provided indexing system yielded 0.10 mm indexing precision. The intrinsic dose distributions indicated that more heterogeneous dose distributions resulted from the use of smaller gantry angle ranges and larger leaf projections. Using 300 degrees gantry angle and 1 cm mode yielded 7% hot and 15% cold spots 7 cm below and above isocenter, respectively. When a 180 degree gantry angle was used, the values changed to 22% hot and 27% cold spots for the same locations. The heterogeneities for the 2 cm mode were 70% greater than the corresponding 1 cm values. CONCLUSIONS: While serial tomotherapy is used to deliver highly conformal dose distributions, significant dosimetric factors must be considered before treatment. The patient must be immobilized during treatment to avoid dose heterogeneities caused by incorrect indexing due to patient movement. Even under ideal conditions, beam divergence can cause significant abutment-region dose heterogeneities. The use of larger gantry angle ranges, smaller leaf widths, and appropriate locations of the gantry rotation axis can minimize these effects.
Equipment Design↗
Evaluation of polymer gels and MRI as a 3-D dosimeter for intensity-modulated radiation therapy.
BANG gel (MGS Research, Inc., Guilford, CT) has been evaluated for measuring intensity-modulated radiation therapy (IMRT) dose distributions. Treatment plans with target doses of 1500 cGy were generated by the Peacock IMRT system (NOMOS Corp., Sewickley, PA) using test target volumes. The gels were enclosed in 13 cm outer diameter cylindrical glass vessels. Dose calibration was conducted using seven smaller (4 cm diameter) cylindrical glass vessels irradiated to 0-1800 cGy in 300 cGy increments. Three-dimensional maps of the proton relaxation rate R2 were obtained using a 1.5 T magnetic resonance imaging (MRI) system (Siemens Medical Systems, Erlangen, Germany) and correlated with dose. A Hahn spin echo sequence was used with TR = 3 s, TE = 20 and 100 ms, NEX = 1, using 1 x 1 x 3 mm3 voxels. The MRI measurements were repeated weekly to identify the gel-aging characteristics. Ionization chamber, thermoluminescent dosimetry (TLD), and film dosimetry measurements of the IMRT dose distributions were obtained to compare against the gel results. The other dosimeters were used in a phantom with the same external cross-section as the gel phantom. The irradiated R2 values of the large vessels did not precisely track the smaller vessels, so the ionization chamber measurements were used to normalize the gel dose distributions. The point-to-point standard deviation of the gel dose measurements was 7.0 cGy. When compared with the ionization chamber measurements averaged over the chamber volume, 1% agreement was obtained. Comparisons against radiographic film dose distribution measurements and the treatment planning dose distribution calculation were used to determine the spatial localization accuracy of the gel and MRI. Spatial localization was better than 2 mm, and the dose was accurately determined by the gel both within and outside the target. The TLD chips were placed throughout the phantom to determine gel measurement precision in high- and low-dose regions. A multidimensional dose comparison tool that simultaneously examines the dose-difference and distance-to-agreement was used to evaluate the gel in both low-and high-dose gradient regions. When 3% and 3 mm criteria were used for the comparisons, more than 90% of the TLD measurements agreed with the gel, with the worst of 309 TLD chip measurements disagreeing by 40% of the criteria. All four MRI measurement session gel-measured dose distributions were compared to evaluate the time behavior of the gel. The low-dose regions were evaluated by comparison with TLD measurements at selected points, while high-dose regions were evaluated by directly comparing measured dose distributions. Tests using the multidimensional comparison tool showed detectable degradation beyond one week postirradiation, but all low-dose measurements passed relative to the test criteria and the dose distributions showed few regions that failed.
Biophysical Phenomena↗
3D treatment planning and intensity-modulated radiation therapy.
Three-dimensional (3D) image-based treatment planning and new delivery technologies have spurred the implementation of external beam radiation therapy techniques, in which the high-dose region is conformed much more closely to the target volume than previously possible, thus reducing the volume of normal tissues receiving a high dose. This form of external beam irradiation is referred to as 3D conformal radiation therapy (3DCRT). 3DCRT is not just an add-on to the current radiation oncology process; it represents a radical change in practice, particularly for the radiation oncologist. Defining target volumes and organs at risk in 3D by drawing contours on CT images on a slice-by-slice basis, as opposed to drawing beam portals on a simulator radiograph, can be challenging, because radiation oncologists are generally not well trained in cross-sectional imaging. Currently, the 3DCRT approach will increase the time and effort required by physicians inexperienced with 3D treatment planning. Intensity-modulated radiation therapy (IMRT) is a more advanced form of 3DCRT, but there is considerable developmental work remaining. The instrumentation and methods used for IMRT quality assurance procedures and testing are not well established. Computer optimization cost functions are too simplistic, and thus time-consuming. Subjective plan evaluation by the radiation oncologist is still the norm. In addition, many fundamental questions regarding IMRT remain unanswered. For example, the radiobiophysical consequences of altered time-dose-fraction are unknown. Also, the fact that there is much greater dose heterogeneity for both the target and normal critical structures with IMRT compared to traditional irradiation techniques challenges current radiation oncology planning principles. However, this new process of planning and treatment delivery shows significant potential for improving the therapeutic ratio. In addition, while inefficient today, these systems, when fully developed, will improve the efficiency with which external beam radiation therapy can be planned and delivered, thus lowering costs.
Humans↗