Helical tomotherapy with simultaneous integrated boost dose painting for the treatment of synchronous primary cancers involving the head and neck.

OBJECTIVE: To demonstrate the feasibility of helical tomotherapy (HT)-based intensity-modulated radiotherapy (IMRT) for the treatment of synchronous primary cancers arising from the head and neck. METHODS: 14 consecutive patients with histologically proven squamous cell carcinoma of the head and neck were determined to have a second primary cancer in the upper aerodigestive tract on further evaluation and were treated with HT using simultaneous integrated boost IMRT. Megavoltage CT scans were acquired daily as part of an image-guided registration protocol. Concurrent platinum-based systemic therapy was given to nine patients (64%). RESULTS: HT resulted in durable local control in 21 of the 28 primary disease sites irradiated, including a complete clinical and radiographic response initially observed at 17 of the 20 sites with gross tumour. The mean displacements to account for interfraction motion were 2.44 ± 1.25, 2.92 ± 1.09 and 2.31 ± 1.70 mm for the medial-lateral (ML), superior-inferior (SI) and anteroposterior (AP) directions, respectively. Table shifts of >3 mm occurred in 19%, 20% and 22% of the ML, SI and AP directions, respectively. The 2-year estimates of overall survival, local-regional control and progression-free survival were 58%, 73% and 60%, respectively. CONCLUSION: The effectiveness of HT for the treatment of synchronous primary cancers of the head and neck was demonstrated. ADVANCES IN KNOWLEDGE: HT is a feasible option for synchronous primary cancers of the head and neck and can result in long-term disease control with acceptable toxicity in appropriately selected patients.

Evaluation of hippocampus dose for patients undergoing intensity-modulated radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the dose received by the hippocampus among patients undergoing intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer. METHODS: 10 patients with biopsy-proven, locally advanced nasopharyngeal cancer constituted the study population. The total prescribed dose to the planning target volume (PTV) was 70 Gy (D95%) delivered in 2.12-Gy daily fractions using IMRT. Using established anatomical guidelines, MRI co-registration and the assistance of a board-certified neuroradiologist, the right and left hippocampi were delineated on axial imaging from the CT scan obtained at simulation for each patient beginning at the most anterior portion of the lateral ventricle. IMRT treatment plans were generated without dose-volume constraints to the hippocampus. A range of dose-volume statistics was calculated. RESULTS: The mean hippocampus volume was 6.01 ± 2.61 cm(3). The mean V20 was 72.2%; V40 was 22.0%; V50 was 10.2%; and V60 was 5.5%. The average mean, minimum and maximum hippocampus doses were 30.27 Gy (range, 19.08-47.99 Gy); 17.54 Gy (range, 11.66-33.17 Gy); and 54.95 Gy (range, 35.59-75.57 Gy), respectively. The hippocampus received a maximum dose exceeding 70 Gy in 30% of cases. CONCLUSION: Our dosimetric analysis suggests that, for patients undergoing IMRT for nasopharyngeal cancer, the hippocampus routinely receives significantly high doses. ADVANCES IN KNOWLEDGE: The hippocampus receives a fair amount of incidental radiation during treatment for nasopharyngeal cancer. Given the importance of this structure with respect to memory and neurocognitive function, consideration should be given to identifying the hippocampus as a critical organ at risk in the IMRT optimization process.

Clinical-dosimetric relationship between lacrimal gland dose and ocular toxicity after intensity-modulated radiotherapy for sinonasal tumours.

OBJECTIVE: To characterise the relationship between lacrimal gland dose and ocular toxicity among patients treated by intensity-modulated radiotherapy (IMRT) for sinonasal tumours. METHODS: 40 patients with cancers involving the nasal cavity and paranasal sinuses were treated with IMRT to a median dose of 66.0 Gy. Toxicity was scored using the Radiation Therapy Oncology Group morbidity criteria based on conjunctivitis, corneal ulceration and keratitis. The paired lacrimal glands were contoured as organs at risk, and the mean dose, maximum dose, V10, V20 and V30 were determined. Statistical analysis was performed using logistic regression and the Akaike information criterion (AIC). RESULTS: The maximum and mean dose to the ipsilateral lacrimal gland were 19.2 Gy (range, 1.4-75.4 Gy) and 14.5 Gy (range, 11.1-67.8 Gy), respectively. The mean V10, V20 and V30 values were 50%, 25% and 17%, respectively. The incidence of acute and late Grade 3+ toxicities was 23% and 19%, respectively. Based on logistic regression and AIC, the maximum dose to the ipsilateral lacrimal gland was identified as a more significant predictor of acute toxicity (AIC, 53.89) and late toxicity (AIC, 32.94) than the mean dose (AIC, 56.13 and 33.83, respectively). The V20 was identified as the most significant predictor of late toxicity (AIC, 26.81). CONCLUSION: A dose-response relationship between maximum dose to the lacrimal gland and ocular toxicity was established. Our data suggesting a threshold relationship may be useful in establishing dosimetric guidelines for IMRT planning that may decrease the risk of acute and late lacrimal toxicities in the future. ADVANCES IN KNOWLEDGE: A threshold relationship between radiation dose to the lacrimal gland and ocular toxicity was demonstrated, which may aid in treatment planning and reducing the morbidity of radiotherapy for sinonasal tumours.

Intensity-modulated radiotherapy for nasopharyngeal carcinoma: improvement of the therapeutic ratio with helical tomotherapy vs segmental multileaf collimator-based techniques.

OBJECTIVES: The aim of the study was to compare differences in dosimetric, clinical and quality-of-life end points among patients treated with helical tomotherapy (HT) and segmental multileaf collimator (SMLC)-based intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma. METHODS: From June 2005 to August 2009, 30 consecutive patients were treated with IMRT for nasopharyngeal carcinoma to a dose of 70 Gy. 14 patients (47%) were treated using HT and 16 (53%) were treated using SMLC-based IMRT. 28 patients (93%) received concurrent chemotherapy. The patients were evenly balanced between the two radiotherapy groups with respect to clinical and pathological characteristics. Median follow-up was 30 months (range, 6-62 months). RESULTS: The 2-year estimates of overall survival, local-regional control and progression-free survival were 81%, 87% and 82%, respectively. There were no significant differences in any of these end points with respect to IMRT technique (p>0.05 for all). Dosimetric analysis revealed that patients treated by HT had significantly improved salivary sparing with respect to mean dose (27.3 vs 34.1 Gy, p=0.03) and volume receiving greater than or equal to 30 Gy (31.7% vs 47.3%, p=0.01) to the contralateral (spared) parotid gland. The incidence of Grade 3+ late xerostomia was 13 and 7% among patients treated with SMLC-based IMRT and HT, respectively (p=0.62). The corresponding proportion of patients who subjectively reported "too little" or "no" saliva at final follow-up was 38% and 7%, respectively (p=0.04). CONCLUSION: The superior dosimetric outcome observed with HT appeared to translate into moderately improved clinical outcomes with respect to salivary sparing. Prospective trials are needed to validate this gain in the therapeutic ratio.

Changes in position and volume of lung cancer target volumes during stereotactic body radiotherapy (SBRT): is image guidance necessary?

The purpose of this study was to analyze inter- and intra-fractional changes in tumor volume with respect to both spatial and volumetric parameters among patients treated by SBRT for lung cancer. Twelve patients (13 tumors) were treated by SBRT with abdominal compression in 3-5 fractions over a 2 week period to a median dose of 60 Gy (range, 48 to 60 Gy). Kilovoltage cone-beam CT (CBCT) was obtained prior to the delivery of each fraction as well as intra-fractionally yielding a total of 55 CBCT scans. All CBCT scans were registered with the planning CT for target alignment and shifts were recorded and analyzed. Retrospectively, gross tumor volume (GTV) was contoured on all CBCT images and compared to initial planning volumes; positional differences were evaluated utilizing directional and vector analysis. Shifts greater than 5 mm were applied inter-fractionally in 6.8% (lateral), 29.5% (longitudinal), and 6.8% (vertical) of all delivered treatments. Using a 10 mm threshold, the corresponding percentages were 2.3%, 13.6%, and 2.3%, respectively. Across all fractions, the calculated inter-fractional shift vectors ranged from 0 to 31.2 mm, with 40.9%, 15.9%, and 11.4% of all fractions having shift vectors≥5 mm, ≥10 mm, and ≥20 mm, respectively. Intra-fractional shifts were also evaluated and found negligible in a small portion of patients evaluated. The mean overall reduction in GTV was 21.1% during SBRT. Significant changes in both position and volume occur during SBRT for lung cancer. Shifts (particularly in the superior-inferior axis) may exceed applied margins and compromise target coverage. Due to the extreme hypofractionation associated with SBRT, inter-fractional image guidance is necessary.

Comparison of IMRT techniques in the radiotherapeutic management of head and neck cancer: is tomotherapy "better" than step-and-shoot IMRT?

Currently, the most common method of delivering intensity-modulated radiotherapy (IMRT) is through step-and-shoot, segmental multi-leaf collimator (SMLC)-based techniques. Although rotational delivery methods such as helical tomotherapy (HT) have been proposed as offering advantages in the treatment of head and neck cancer, a lack of clinical data exists on its potential utility. This study compared dosimetric, clinical, and quality-of-life endpoints among 149 patients treated by HT and SMLC-IMRT for head and neck cancer. Dosimetric analysis revealed that the use of HT resulted in significant improvements with respect to mean dose (23.5 versus 27.9 Gy, p = 0.03) and V30 (30.1 versus 43.9 Gy, p = 0.01) to the contralateral (spared) parotid gland. However, the incidence of grade 3+ xerostomia in the late setting was 10% and 8% among patients treated by HT and SMLC-IMRT, respectively (p = 0.46). There were no significant differences in any of the quality of life endpoints among patients treated by HT and SMLC-IMRT (p > 0.05, for all). Acknowledging the biases inherent in this retrospective analysis, we found that the dosimetric advantages observed with HT compared to SMLC-IMRT failed to translate into significant improvements in clinical outcome. Prospective studies are needed to further evaluate how HT may affect the therapeutic ratio.

Intensity-modulated radiotherapy increases dose to the brachial plexus compared with conventional radiotherapy for head and neck cancer.

OBJECTIVE: The preferential use of intensity-modulated radiotherapy (IMRT) over conventional radiotherapy (CRT) in the treatment of head and neck cancer has raised concerns regarding dose to non-target tissue. The purpose of this study was to compare dose-volume characteristics with the brachial plexus between treatment plans generated by IMRT and CRT using several common treatment scenarios. METHOD: The brachial plexus was delineated on radiation treatment planning CT scans from 10 patients undergoing IMRT for locally advanced head and neck cancer using a Radiation Therapy Oncology Group-endorsed atlas. No brachial plexus constraint was used. For each patient, a conventional three-field shrinking-field plan was generated and the dose-volume histogram (DVH) for the brachial plexus was compared with that of the IMRT plan. RESULTS: The mean irradiated volumes of the brachial plexus using the IMRT vs the CRT plan, respectively, were as follows: V50 (18±5 ml) vs (11±6 ml), p = 0.01; V60 (6±4 ml) vs (3±3 ml), p = 0.02; V66 (3±1 ml) vs (1±1 ml), p = 0.04, V70 (0±1 ml) vs (0±1 ml), p = 0.68. The maximum point dose to the brachial plexus was 68.9 Gy (range 62.3-78.7 Gy) and 66.1 Gy (range 60.2-75.6 Gy) for the IMRT and CRT plans, respectively (p = 0.01). CONCLUSION: Dose to the brachial plexus is significantly increased among patients undergoing IMRT compared with CRT for head and neck cancer. Preliminary studies on brachial plexus-sparing IMRT are in progress.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).