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Biomedical subjects

Isaac Rosen

Publications and source records attributed to Isaac Rosen.

11 recordsLinked to original sources

Intensity-modulated radiation therapy (IMRT) of cancers of the head and neck: comparison of split-field and whole-field techniques.

BACKGROUND: Oropharynx cancers treated with intensity-modulated radiation (IMRT) are often treated with a monoisocentric or half-beam technique (HB). IMRT is delivered to the primary tumor and upper neck alone, while the lower neck is treated with a matching anterior beam. Because IMRT can treat the entire volume or whole field (WF), the primary aim of the study was to test the ability to plan cases using WF-IMRT while obtaining an optimal plan and acceptable dose distribution and also respecting normal critical structures. METHODS AND MATERIALS: Thirteen patients with early-stage oropharynx cancers had treatment plans created with HB-IMRT and WF-IMRT techniques. Plans were deemed acceptable if they met the planning guidelines (as defined or with minor violations) of the Radiation Therapy Oncology Group protocol H0022. Comparisons included coverage to the planning target volume (PTV) of the primary (PTV66) and subclinical disease (PTV54). We also compared the ability of both techniques to respect the tolerance of critical structures. RESULTS: The volume of PTV66 treated to >110% was less in 9 of the 13 patients in the WF-IMRT plan as compared to the HB-IMRT plan. The calculated mean volume receiving >110% for all patients planned with WF-IMRT was 9.3% (0.8%-25%) compared to 13.7% (2.7%-23.7%) with HB-IMRT (p = 0.09). The PTV54 volume receiving >110% of dose was less in 10 of the 13 patients planned with WF-IMRT compared to HB-IMRT. The mean doses to all critical structures except the larynx were comparable with each plan. The mean dose to the larynx was significantly less (p = 0.001), 18.7 Gy, with HB-IMRT compared to 47 Gy with WF-IMRT. CONCLUSIONS: Regarding target volumes, acceptable plans can be generated with either WF-IMRT or HB-IMRT. WF-IMRT has an advantage if uncertainty at the match line is a concern, whereas HB-IMRT, particularly in cases not involving the base of tongue, can achieve much lower doses to the larynx.

Clinical Trials, Phase I as Topic↗

Interactively exploring optimized treatment plans.

PURPOSE: A new paradigm for treatment planning is proposed that embodies the concept of interactively exploring the space of optimized plans. In this approach, treatment planning ignores the details of individual plans and instead presents the physician with clinical summaries of sets of solutions to well-defined clinical goals in which every solution has been optimized in advance by computer algorithms. METHODS AND MATERIALS: Before interactive planning, sets of optimized plans are created for a variety of treatment delivery options and critical structure dose-volume constraints. Then, the dose-volume parameters of the optimized plans are fit to linear functions. These linear functions are used to show in real time how the target dose-volume histogram (DVH) changes as the DVHs of the critical structures are changed interactively. A bitmap of the space of optimized plans is used to restrict the feasible solutions. The physician selects the critical structure dose-volume constraints that give the desired dose to the planning target volume (PTV) and then those constraints are used to create the corresponding optimized plan. RESULTS: The method is demonstrated using prototype software, Treatment Plan Explorer (TPEx), and a clinical example of a patient with a tumor in the right lung. For this example, the delivery options included 4 open beams, 12 open beams, 4 wedged beams, and 12 wedged beams. Beam directions and relative weights were optimized for a range of critical structure dose-volume constraints for the lungs and esophagus. Cord dose was restricted to 45 Gy. Using the interactive interface, the physician explored how the tumor dose changed as critical structure dose-volume constraints were tightened or relaxed and selected the best compromise for each delivery option. The corresponding treatment plans were calculated and compared with the linear parameterization presented to the physician in TPEx. The linear fits were best for the maximum PTV dose and worst for the minimum PTV dose. Based on the root-mean-square error between the fit values and their corresponding data values, the linear fit appears to be adequate, although higher order polynomials could give better results. Some of the variance in fit is due to the stochastic nature of the simulated annealing optimization algorithm, which does not reproduce the exact same results in repetitions of the same calculation. Using a directed search algorithm for plan optimization should produce better parameter fits and, therefore, better predictions of plan characteristics by TPEx. CONCLUSIONS: Using TPEx, the physician can easily select the optimum plan for a patient, with no imposed arbitrary definition of the "best" plan. More importantly, the physician can readily see what can be achieved for the patient with a given delivery technique. There is no more uncertainty about whether or not a better plan exists. By comparing the "best" plans for different delivery options (e.g., three-dimensional conformal radiotherapy versus intensity-modulated radiation therapy), the physician can gauge the clinical benefits of greater technical complexity. However, before the TPEx process can be clinical useful, faster computers and/or algorithms are needed and more studies are needed to better model the spaces of optimized solutions.

Algorithms↗

The delivery of IMRT with a single physical modulator for multiple fields: a feasibility study for paranasal sinus cancer.

PURPOSE: This study describes a new intensity-modulated radiation therapy (IMRT) delivery method that utilizes a single modulator to deliver multiple fields ("multifield modulator"). This technique reduces the treatment time and manufacturing costs typically associated with modulator-IMRT. Technical feasibility was evaluated for treating paranasal sinus cancers. METHODS AND MATERIALS: Technical feasibility was measured by three criteria: The dose distributions of the multifield modulator-IMRT plans should offer improvements over those produced by 3D conformal plans and be equivalent to those of step-and-shoot multileaf collimator (MLC) IMRT plans, the manufactured modulators should meet quality assurance specifications, and the effort required to use this technology should not substantially exceed the effort required for current IMRT practice. Seven paranasal cancer cases were examined. The Wilcoxon signed rank test was used for statistical analysis. RESULTS: Multifield modulator-IMRT plans can improve target coverage while reducing critical structure doses compared to 3D conformal plans. Multifield modulator-IMRT plans are at least equivalent to the corresponding step-and-shoot MLC-IMRT plans. Multifield modulators can be constructed to meet design specifications in quality assurance tests. The time required for manufacturing, quality assurance, and treatment delivery using multifield modulators was measured and found to be only slightly greater than that for current IMRT treatment methods. CONCLUSIONS: IMRT treatments using multifield modulators for paranasal sinus tumors are feasible. Clinics may find it worthwhile to commit the minimal extra time for quality assurance and treatment to benefit from the improved dose distribution and lack of interplay between MLC leaf motion and internal target motion.

Feasibility Studies↗

Hazards of dose escalation in prostate cancer radiotherapy.

PURPOSE: To assess the benefit of escalating the dose in definitive prostate cancer radiotherapy vs. the associated risk of complications. MATERIALS AND METHODS: Between 1987 and 1999, 1087 patients with clinical Stage T1b-T3 adenocarcinoma of the prostate were definitively irradiated without hormonal therapy and had a pretreatment serum prostate-specific antigen (PSA) and Gleason score recorded. The median follow-up was 65 months. Doses ranged from 64 to 78 Gy, with the treatment techniques corresponding to the year of therapy and the prescribed dose. A total of 301 patients were treated on a randomized protocol to either 70 or 78 Gy. Also, 163 patients were treated with three-dimensional conformal therapy and had dose-volume histograms available for review. RESULTS: Tumor stage, grade, pretreatment PSA level, and radiation dose were all independent predictors of PSA disease-free survival (PSA-DFS) in multivariate analysis. The hazard rate for biochemical failure peaked at 1.5-3 years after radiotherapy. Although a statistically significant dose effect on PSA-DFS was found in the pretreatment PSA levels of those with both < or =10 ng/mL and >10 ng/mL, in those with a pretreatment PSA < or =10 ng/mL, the improvement in outcome was only seen going from a dose level of 64-66 Gy to 68-70 Gy with a 5-year PSA-DFS rate of 66% vs. 81% (p <0.0001). This was also confirmed by the data from the randomized patients who showed no difference in outcome whether treated to 70 Gy or 78 Gy. In patients with a pretreatment PSA level >10 ng/mL, a statistically significant improvement was found in disease-free outcome among the 64-66-Gy, 68-70-Gy, and 78-Gy levels. PSA-DFS was approximately 50% better at each higher dose level at 5 and 8 years after treatment. The dose had a statistically significant impact in both intermediate- and high-risk groups. Rectal morbidity was both dose and volume related. Although at 5 years after therapy, the Grade 2-3 rectal complication rate was twice as high for patients treated to 78 Gy than to 70 Gy, 26% vs. 12%, this risk could be markedly diminished by adhering to dose-volume constraints. CONCLUSIONS: In intermediate- and high-risk prostate cancer patients, although it appears that radiation-dose escalation may improve PSA-DF outcome, the price paid in treatment morbidity can be high without adequate attention to dose-volume constraints of normal tissue. Care must be taken to consider not only the hazard of tumor recurrence but also that of complications.

Adenocarcinoma↗

Patient-specific point dose measurement for IMRT monitor unit verification.

PURPOSE: To review intensity-modulated radiation therapy (IMRT) monitor unit verification in a phantom for 751 clinical cases. METHODS AND MATERIALS: A custom water-filled phantom was used to measure the integral dose with an ion chamber for patient-specific quality assurance. The Corvus IMRT planning system was used for all cases reviewed. The 751 clinical cases were classified into 9 treatment sites: central nervous system (27 cases), gastrointestinal (24 cases), genitourinary (447 cases), gynecologic (18 cases), head and neck (200 cases), hematology (12 cases), pediatric (3 cases), sarcoma (8 cases), and thoracic (12 cases). Between December 1998 and January 2002, 1591 measurements were made for these 751 IMRT quality assurance plans. RESULTS: The mean difference (MD) in percent between the measurements and the calculations was +0.37% (with the measurement being slightly higher). The standard deviation (SD) was 1.7%, and the range of error was from -4.5% to 9.5%. The MD and SD were +0.49% and 1.4% for MIMiC treatments delivered in 2-cm mode (261 cases) and -0.33% and 2.7% for those delivered in 1-cm mode (36 cases). Most treatments (420) were delivered using the step-and-shoot multileaf collimator with a 6-MV photon beam; the MD and SD were +0.31% and 1.8%, respectively. Among the 9 treatment sites, the prostate IMRT (in genitourinary site) was most consistent with the smallest SD (1.5%). There were 23 cases (3.1% of all cases) in which the measurement difference was greater than 3.5%; of those, 6 cases used the MIMiC in 1-cm mode, and 14 of the cases were from the head-and-neck treatment site. CONCLUSION: IMRT monitor unit calculations from the Corvus planning system agreed within 3.5% with the point-dose ion chamber measurement in 97% of 751 cases representing 9 different treatment sites. A good consistency was observed across sites.

Algorithms↗

Experience of ultrasound-based daily prostate localization.

PURPOSE: The NOMOS (Sewickley, PA) B-mode Acquisition and Targeting System (BAT) ultrasound system provides a rapid means of correcting for interfraction prostate positional variation. In this investigation, we report our experience on the clinical issues relevant to the daily use of the BAT system and the analysis of combined setup error and organ motion for 3509 BAT alignment procedures in 147 consecutive patients treated with IMRT for prostate cancer. METHODS AND MATERIALS: After setup to external skin marks, therapists performed the BAT ultrasound alignment procedure before each IMRT treatment. In this study, a single physician (A.C.) reviewed all BAT images and classified image quality and accuracy of image alignment by the therapist. On a scale of 1-3, near-perfect image quality or alignment was given a 1, fair image quality or misalignment > or = 5 mm (likely within the PTV) was given a 2, and unacceptable image quality or misalignment >5 mm (potential to violate the PTV) was given a value of 3. The distribution of shifts made was analyzed in each dimension and for all patients. The time required to perform the BAT alignment was also assessed in 17 patients. RESULTS: Among the 3509 attempted BAT procedures, the image quality was judged to be poor or unacceptable in 5.1% (181). Of the remaining 3328 BAT images, with quality scores of 1-2, alignments were unacceptable (>5 mm misalignment as judged by the reviewing physician) in 3% (100). The mean shift in each direction, averaged over all patients, was 0.5-0.7 mm. Interfraction standard deviation (1 SD) of prostate position based on combined setup error and internal organ motion is 4.9 mm, 4.4 mm, and 2.8 mm in the anteroposterior (AP), superior-inferior (SI), and lateral (RL) dimensions, respectively. The distribution of the shifts was a near-random Gaussian-type in all three major axes, with greater variations in AP and SI directions. The percent of BAT procedures in which the shift was >5 mm was 28.6% in AP, 23% in SI, and 9% in RL directions. The average BAT procedure took extra 5 min out of a 20-min time slot in a typical eight-field IMRT treatment. CONCLUSIONS: The quality of the daily ultrasound images was deemed acceptable in 95%. Major alignment errors by therapists were only 3%. The BAT system is clinically effective and feasible in a matter of 5 min. Although the accuracy of the BAT was not addressed in this investigation, we found a significant percentage of large shifts being made from the initial alignment position.

Humans↗

Evaluation of mechanical precision and alignment uncertainties for an integrated CT/LINAC system.

A new integrated CT/LINAC combination, in which the CT scanner is inside the radiation therapy treatment room and the same patient couch is used for CT scanning and treatment (after a 180-degree couch rotation), should allow for accurate correction of interfractional setup errors. The purpose of this study was to evaluate the sources of uncertainties, and to measure the overall precision of this system. The following sources of uncertainty were identified: (1) the patient couch position on the LINAC side after a rotation, (2) the patient couch position on the CT side after a rotation, (3) the patient couch position as indicated by its digital readout, (4) the difference in couch sag between the CT and LINAC positions, (5) the precision of the CT coordinates, (6) the identification of fiducial markers from CT images, (7) the alignment of contours with structures in the CT images, and (8) the alignment with setup lasers. The largest single uncertainties (one standard deviation or 1 SD) were found in couch position on the CT side after a rotation (0.5 mm in the RL direction) and the alignment of contours with the CT images (0.4 mm in the SI direction). All other sources of uncertainty are less than 0.3 mm (1 SD). The overall precision of two setup protocols was investigated in a controlled phantom study. A protocol that relies heavily on the mechanical integrity of the system, and assumes a fixed relationship between the LINAC isocenter and the CT images, gave a predicted precision (1 SD) of 0.6, 0.7, and 0.6 mm in the SI, RL and AP directions, respectively. The second protocol reduces reliance on the mechanical precision of the total system, particularly the patient couch, by using radio-opaque fiducial markers to transfer the isocenter information from the LINAC side to the CT images. This protocol gave a slightly improved predicted precision of 0.5, 0.4, and 0.4 mm in the SI, RL and AP directions, respectively. The distribution of phantom position after CT-based correction confirmed these results. Knowledge of the individual sources of uncertainty will allow alternative setup protocols to be evaluated in the future without the need for significant additional measurements.

Artifacts↗

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.

Algorithms↗

Late rectal toxicity: dose-volume effects of conformal radiotherapy for prostate cancer.

PURPOSE: To identify dosimetric, anatomic, and clinical factors that correlate with late rectal toxicity after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. METHODS AND MATERIALS: We retrospectively analyzed the dose-volume histograms and clinical records of 163 Stage T1b-T3c prostate cancer patients treated between 1992 and 1999 with 3D-CRT, to a total isocenter dose of 74-78 Gy at The University of Texas M. D. Anderson Cancer Center. The median follow-up was 62 months (range 24-102). All late rectal complications were scored using modified Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. The 6-year toxicity rate was assessed using Kaplan-Meier analysis and the log-rank test. A univariate proportional hazards regression model was used to test the correlation between Grade 2 or higher toxicity and the dosimetric, anatomic, and clinical factors. In a multivariate regression model, clinical factors were added to the dosimetric and anatomic variables to determine whether they significantly altered the risk of developing late toxicity. RESULTS: At 6 years, the rate of developing Grade 2 or higher late rectal toxicity was 25%. A significant volume effect was observed at rectal doses of 60, 70, 75.6, and 78 Gy, and the risk of developing rectal complications increased exponentially as greater volumes were irradiated. Although the percentage of rectal volume treated correlated significantly with the incidence of rectal complications at all dose levels (p <0.0001 for all comparisons), the absolute rectal volume appeared to be a factor only at the higher doses of 70, 75.6, and 78 Gy (p = 0.0514, 0.0016, and 0.0021, respectively). The following variables also correlated with toxicity on the univariate analysis: maximal dose to the clinical target volume, maximal dose to rectum, maximal dose to the rectum as a percentage of the prescribed dose, and maximal dose delivered to 10 cm(3) of the rectum. Of the clinical variables tested, only a history of hemorrhoids correlated with rectal toxicity (p = 0.003). Multivariate analysis showed that the addition of hemorrhoids increased the risk of toxicity for each dosimetric variable found to be significant on univariate analysis (p <0.05 for all comparisons). CONCLUSION: Dose-volume histogram analyses clearly indicated a volume effect on the probability of developing late rectal complications. Therefore, dose escalation may be safely achieved by adherence to dose-volume histogram constraints during treatment planning and organ localization at the time of treatment to ensure consistent patient setup.

Aged↗

Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial.

PURPOSE: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. METHODS AND MATERIALS: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. RESULTS: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA 10 ng/mL who were treated to 78 Gy (98% vs. 88% at 6 years, p = 0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12% and 26% for the 70 Gy and 78 Gy arms, respectively (p = 0.001). Grade 2 or higher bladder complications were similar at 10%. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy. CONCLUSION: An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives >or=70 Gy to <25% should be used.

Aged↗