Daniel A. Low

A technique for the quantitative evaluation of dose distributions

The commissioning of a three-dimensional treatment planning system requires comparisons of measured and calculated dose distributions. Techniques have been developed to facilitate quantitative comparisons, including superimposed isodoses, dose-difference, and distance-to-agreement (DTA) distributions. The criterion for acceptable calculation performance is generally defined as a tolerance of the dose and DTA in regions of low and high dose gradients, respectively. The dose difference and DTA distributions complement each other in their useful regions. A composite distribution has recently been developed that presents the dose difference in regions that fail both dose-difference and DTA comparison criteria. Although the composite distribution identifies locations where the calculation fails the preselected criteria, no numerical quality measure is provided for display or analysis. A technique is developed to unify dose distribution comparisons using the acceptance criteria. The measure of acceptability is the multidimensional distance between the measurement and calculation points in both the dose and the physical distance, scaled as a fraction of the acceptance criteria. In a space composed of dose and spatial coordinates, the acceptance criteria form an ellipsoid surface, the major axis scales of which are determined by individual acceptance criteria and the center of which is located at the measurement point in question. When the calculated dose distribution surface passes through the ellipsoid, the calculation passes the acceptance test for the measurement point. The minimum radial distance between the measurement point and the calculation points (expressed as a surface in the dose-distance space) is termed the gamma index. Regions where gamma > 1 correspond to locations where the calculation does not meet the acceptance criteria. The determination of gamma throughout the measured dose distribution provides a presentation that quantitatively indicates the calculation accuracy. Examples of a 6 MV beam penumbra are used to illustrate the gamma index.

Guidance document on delivery, treatment planning, and clinical implementation of IMRT : Report of the IMRT subcommittee of the AAPM radiation therapy committee

Intensity-modulated radiation therapy (IMRT) represents one of the most significant technical advances in radiation therapy since the advent of the medical linear accelerator. It allows the clinical implementation of highly conformal nonconvex dose distributions. This complex but promising treatment modality is rapidly proliferating in both academic and community practice settings. However, these advances do not come without a risk. IMRT is not just an add-on to the current radiation therapy process; it represents a new paradigm that requires the knowledge of multimodality imaging, setup uncertainties and internal organ motion, tumor control probabilities, normal tissue complication probabilities, three-dimensional (3-D) dose calculation and optimization, and dynamic beam delivery of nonuniform beam intensities. Therefore, the purpose of this report is to guide and assist the clinical medical physicist in developing and implementing a viable and safe IMRT program. The scope of the IMRT program is quite broad, encompassing multileaf-collimator-based IMRT delivery systems, goal-based inverse treatment planning, and clinical implementation of IMRT with patient-specific quality assurance. This report, while not prescribing specific procedures, provides the framework and guidance to allow clinical radiation oncology physicists to make judicious decisions in implementing a safe and efficient IMRT program in their clinics.

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 patients 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.

Evaluation of the gamma dose distribution comparison method

The gamma tool was developed to quantitatively compare dose distributions, either measured or calculated. Before computing gamma, the dose and distance scales of the two distributions, referred to as evaluated and reference, are renormalized by dose and distance criteria, respectively. The renormalization allows the dose distribution comparison to be conducted simultaneously along dose and distance axes. The gamma quantity, calculated independently for each reference point, is the minimum distance in the renormalized multidimensional space between the evaluated distribution and the reference point. The gamma quantity degenerates to the dose-difference and distance-to-agreement tests in shallow and very steep dose gradient regions, respectively. Since being introduced, the gamma quantity has been used by investigators to evaluate dose calculation algorithms, and compare dosimetry measurements. This manuscript examines the gamma distribution behavior in two dimensions and evaluates the gamma distribution in the presence of data noise. Noise in the evaluated distribution causes the gamma distribution to be underestimated relative to the no-noise, condition. Noise in the reference distribution adds noise in the gamma distribution in proportion to the normalized dose noise. In typical clinical use, the fraction of points that exceed 3% and 3 mm can be extensive, so we typically use 5% and 2-3 mm in clinical evaluations. For clinical cases, the calculation time is typically 5 minutes for a 1 x 1 mm2 interpolated resolution on an 800 MHz Pentium 4 for a 14.1 x 15.2 cm2 radiographic film.

A method for the reconstruction of four-dimensional synchronized CT scans acquired during free breathing

Breathing motion is a significant source of error in radiotherapy treatment planning for the thorax and upper abdomen. Accounting for breathing motion has a profound effect on the size of conformal radiation portals employed in these sites. Breathing motion also causes artifacts and distortions in treatment planning computed tomography (CT) scans acquired during free breathing and also causes a breakdown of the assumption of the superposition of radiation portals in intensity-modulated radiation therapy, possibly leading to significant dose delivery errors. Proposed voluntary and involuntary breath-hold techniques have the potential for reducing or eliminating the effects of breathing motion, however, they are limited in practice, by the fact that many lung cancer patients cannot tolerate holding their breath. We present an alternative solution to accounting for breathing motion in radiotherapy treatment planning, where multislice CT scans are collected simultaneously with digital spirometry over many free breathing cycles to create a four-dimensional (4-D) image set, where tidal lung volume is the additional dimension. An analysis of this 4-D data leads to methods for digital-spirometry, based elimination or accounting of breathing motion artifacts in radiotherapy treatment planning for free breathing patients. The 4-D image set is generated by sorting free-breathing multislice CT scans according to user-defined tidal-volume bins. A multislice CT scanner is operated in the ciné mode, acquiring 15 scans per couch position, while the patient undergoes simultaneous digital-spirometry measurements. The spirometry is used to retrospectively sort the CT scans by their correlated tidal lung volume within the patients normal breathing cycle. This method has been prototyped using data from three lung cancer patients. The actual tidal lung volumes agreed with the specified bin volumes within standard deviations ranging between 22 and 33 cm3. An analysis of sagittal and coronal images demonstrated relatively small (<1 cm) motion artifacts along the diaphragm, even for tidal volumes where the rate of breathing motion is greatest. While still under development, this technology has the potential for revolutionizing the radiotherapy treatment planning for the thorax and upper abdomen.

Patterns of failure in patients receiving definitive and postoperative IMRT for head-and-neck cancer.

PURPOSE To analyze the patterns of locoregional failure in patients with head-and-neck cancer treated with inverse planning intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS Between February 1997 and December 2000, 165 patients with histologically confirmed head-and-neck cancer were treated using a parotid-sparing inverse planning IMRT protocol. Thirty-nine patients who received either palliative repeat irradiation or IMRT as a boost were excluded from this analysis, leaving 126 patients for this analysis. Of the 126 patients, 30 were women and 96 were men (median age 56 years, range 13-84). Fifty-two patients (41%) received definitive IMRT. Of the 52 patients, 17 were treated with RT alone and 35 with concurrent cisplatin-based chemotherapy regimens. Seventy-four patients (59%) received postoperative IMRT. The median follow-up was 26 months (range 12-55). IMRT was used only in the upper neck for salivary sparing. The lower neck was treated with a conventional AP low-neck port abutted to the inferior IMRT dose distribution border. The radiation dose was prescribed to the two clinical target volumes (CTVs) according to the assumed risk of containing disease. The mean dose for definitive IMRT patients was 72.64 +/- 4.83 Gy to CTV1 and 64.34 +/- 5.15 Gy to CTV2. The mean dose to CTV1 and CTV2 in postoperative cases was 68.53 +/- 4.71 Gy and 60.95 +/- 5.33 Gy, respectively. The locations of failure were analyzed. RESULTS Seventeen locoregional failures (persistent or recurrent disease) were found. Of these 17 failures, 9 (53%) were inside CTV1. One failure (6%) was marginal to CTV1 but inside CTV2. One failure (6%) occurred outside CTV1 but inside CTV2. Another failure was marginal to CTV2. Of the 17 failures, 5 (28%) were found outside of the IMRT field and in the lower neck. Dose-volume histogram analysis revealed that for all but 1 patient, the recurrent/persistent disease within the CTVs received comparable or superior dose coverage relative to the CTV. The 2-year actuarial locoregional control rate was 85%, and the ultimate locoregional control rate after surgical salvage was 89%. We observed no dermal failure and only one marginal failure in the region adjacent to the spared parotid glands. CONCLUSION We have shown that the target definition and coverage for patients treated with IMRT for parotid sparing is adequate. The predominant tumor failure within CTV1 may imply the need to identify patients with radioresistant tumor subvolumes (such as hypoxic regions) within the CTV. This information would assist in discriminating a subgroup of tumors for a more aggressive and target-specific therapeutic approach.

Intensity-modulated radiation therapy (IMRT) reduces small bowel, rectum, and bladder doses in patients with cervical cancer receiving pelvic and para-aortic irradiation.

PURPOSE The emergent use of combined modality approach (chemotherapy and radiation therapy) for the treatment of patients with cervical cancer is associated with significant gastrointestinal and genitourinary toxicity. Intensity-modulated radiation therapy (IMRT) has the potential to deliver adequate dose to the target structures while sparing the normal organs and could also allow for dose escalation to grossly enlarged metastatic lymph node in pelvic or para-aortic area without increasing gastrointestinal/genitourinary complications. We conducted a dosimetric analysis to determine if IMRT can meet these objectives in the treatment of cervical cancer. METHODS AND MATERIALS Computed tomography scan studies of 10 patients with cervical cancer were retrieved and used as anatomic references for planning. Upon the completion of target and critical structure delineation, the imaging and contour data were transferred to both an IMRT planning system (Corvus, Nomos) and a three-dimensional planning system (Focus, CMS) on which IMRT as well as conventional planning with two- and four-field techniques were derived. Treatment planning was done on these two systems with uniform prescription, 45 Gy in 25 fractions to the uterus, the cervix, and the pelvic and para-aortic lymph nodes. Normalization was done to all IMRT plans to obtain a full coverage of the cervix with the 95% isodose curve. Dose-volume histograms were obtained for all the plans. A Students t test was performed to compute the statistical significance. RESULTS The volume of small bowel receiving the prescribed dose (45 Gy) with IMRT technique was as follows: four fields, 11.01 +/- 5.67%; seven fields, 15.05 +/- 6.76%; and nine fields, 13.56 +/- 5.30%. These were all significantly better than with two-field (35.58 +/- 13.84%) and four-field (34.24 +/- 17.82%) conventional techniques (p < 0.05). The fraction of rectal volume receiving a dose greater than the prescribed dose was as follows: four fields, 8.55 +/- 4.64%; seven fields, 6.37 +/- 5.19%; nine fields, 3.34 +/- 3.0%; in contrast to 84.01 +/- 18.37% with two-field and 46.37 +/- 24.97% with four-field conventional technique (p < 0.001). The fractional volume of bladder receiving the prescribed dose and higher was as follows: four fields, 30.29 +/- 4.64%; seven fields, 31.66 +/- 8.26%; and nine fields, 26.91 +/- 5.57%. It was significantly worse with the two-field (92.89 +/- 35.26%) and with the four-field (60.48 +/- 31.80%) techniques (p < 0.05). CONCLUSION In this dosimetric study, we demonstrated that with similar target coverage, normal tissue sparing is superior with IMRT in the treatment of cervical cancer.

Dosimetry tools and techniques for IMRT

Intensity modulated radiation therapy (IMRT) poses a number of challenges for properly measuring commissioning data and quality assurance (QA) radiation dose distributions. This report provides a comprehensive overview of how dosimeters, phantoms, and dose distribution analysis techniques should be used to support the commissioning and quality assurance requirements of an IMRT program. The proper applications of each dosimeter are described along with the limitations of each system. Point detectors, arrays, film, and electronic portal imagers are discussed with respect to their proper use, along with potential applications of 3D dosimetry. Regardless of the IMRT technique utilized, some situations require the use of multiple detectors for the acquisition of accurate commissioning data. The overall goal of this task group report is to provide a document that aids the physicist in the proper selection and use of the dosimetry tools available for IMRT QA and to provide a resource for physicists that describes dosimetry measurement techniques for purposes of IMRT commissioning and measurement-based characterization or verification of IMRT treatment plans. This report is not intended to provide a comprehensive review of commissioning and QA procedures for IMRT. Instead, this report focuses on the aspects of metrology, particularly the practical aspects of measurements that are unique to IMRT. The metrology of IMRT concerns the application of measurement instruments and their suitability, calibration, and quality control of measurements. Each of the dosimetry measurement tools has limitations that need to be considered when incorporating them into a commissioning process or a comprehensive QA program. For example, routine quality assurance procedures require the use of robust field dosimetry systems. These often exhibit limitations with respect to spatial resolution or energy response and need to themselves be commissioned against more established dosimeters. A chain of dosimeters, from secondary standards to field instruments, is established to assure the quantitative nature of the tests. This report is intended to describe the characteristics of the components of these systems; dosimeters, phantoms, and dose evaluation algorithms. This work is the report of AAPM Task Group 120.

A comparison between amplitude sorting and phase-angle sorting using external respiratory measurement for 4D CT

Respiratory motion can cause significant dose delivery errors in conformal radiation therapy for thoracic and upper abdominal tumors. Four-dimensional computed tomography (4D CT) has been proposed to provide the image data necessary to model tumor motion and consequently reduce these errors. The purpose of this work was to compare 4D CT reconstruction methods using amplitude sorting and phase angle sorting. A 16-slice CT scanner was operated in ciné mode to acquire 25 scans consecutively at each couch position through the thorax. The patient underwent synchronized external respiratory measurements. The scans were sorted into 12 phases based, respectively, on the amplitude and direction (inhalation or exhalation) or on the phase angle (0-360 degrees) of the external respiratory signal. With the assumption that lung motion is largely proportional to the measured respiratory amplitude, the variation in amplitude corresponds to the variation in motion for each phase. A smaller variation in amplitude would associate with an improved reconstructed image. Air content, defined as the amount of air within the lungs, bronchi, and trachea in a 16-slice CT segment and used by our group as a surrogate for internal motion, was correlated to the respiratory amplitude and phase angle throughout the lungs. For the 35 patients who underwent quiet breathing, images (similar to those used for treatment planning) and animations (used to display respiratory motion) generated using amplitude sorting displayed fewer reconstruction artifacts than those generated using phase angle sorting. The variations in respiratory amplitude were significantly smaller (P < 0.001) with amplitude sorting than those with phase angle sorting. The subdivision of the breathing cycle into more (finer) phases improved the consistency in respiratory amplitude for amplitude sorting, but not for phase angle sorting. For 33 of the 35 patients, the air content showed significantly improved (P < 0.001) correlation with the respiratory amplitude than with the phase angle, suggesting a stronger relationship between internal motion and amplitude. Overall, amplitude sorting performed better than phase angle sorting for 33 of the 35 patients and equally well for two patients who were immobilized with a stereotactic body frame and an abdominal compression plate.

EXPERIENCE-BASED QUALITY CONTROL OF CLINICAL INTENSITY-MODULATED RADIOTHERAPY PLANNING

PURPOSE To incorporate a quality control tool, according to previous planning experience and patient-specific anatomic information, into the intensity-modulated radiotherapy (IMRT) plan generation process and to determine whether the tool improved treatment plan quality. METHODS AND MATERIALS A retrospective study of 42 IMRT plans demonstrated a correlation between the fraction of organs at risk (OARs) overlapping the planning target volume and the mean dose. This yielded a model, predicted dose = prescription dose (0.2 + 0.8 [1 - exp(-3 overlapping planning target volume/volume of OAR)]), that predicted the achievable mean doses according to the planning target volume overlap/volume of OAR and the prescription dose. The model was incorporated into the planning process by way of a user-executable script that reported the predicted dose for any OAR. The script was introduced to clinicians engaged in IMRT planning and deployed thereafter. The scripts effect was evaluated by tracking δ = (mean dose-predicted dose)/predicted dose, the fraction by which the mean dose exceeded the model. RESULTS All OARs under investigation (rectum and bladder in prostate cancer; parotid glands, esophagus, and larynx in head-and-neck cancer) exhibited both smaller δ and reduced variability after script implementation. These effects were substantial for the parotid glands, for which the previous δ = 0.28 ± 0.24 was reduced to δ = 0.13 ± 0.10. The clinical relevance was most evident in the subset of cases in which the parotid glands were potentially salvageable (predicted dose <30 Gy). Before script implementation, an average of 30.1 Gy was delivered to the salvageable cases, with an average predicted dose of 20.3 Gy. After implementation, an average of 18.7 Gy was delivered to salvageable cases, with an average predicted dose of 17.2 Gy. In the prostate cases, the rectum model excess was reduced from δ = 0.28 ± 0.20 to δ = 0.07 ± 0.15. On surveying dosimetrists at the end of the study, most reported that the script both improved their IMRT planning (8 of 10) and increased their efficiency (6 of 10). CONCLUSIONS This tool proved successful in increasing normal tissue sparing and reducing interclinician variability, providing effective quality control of the IMRT plan development process.