Biomedical subjects

Radhe Mohan

Publications and source records attributed to Radhe Mohan.

At least 55 records · Page 3Linked to original sources

PubMed2004

Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas: II--clinical results.

PURPOSE: To perform a Phase I radiation dose-escalation trial to determine the maximal tolerable dose (MTD) deliverable to the gross tumor volume (GTV) using an accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole therapy in the treatment of locally advanced head-and-neck squamous cell carcinoma. The primary objective was the definition of the MTD using established criteria of quantifying acute dose-limiting toxicity (DLT). Secondary objectives included analysis of failure patterns, tumor control rates, and toxicity. METHODS AND MATERIALS: Between July 1999 and June 2002, eligible patients with bulky Stage II to Stage IVB head-and-neck squamous cell carcinoma, excluding laryngeal primaries, were enrolled. Intensity-modulated radiotherapy was delivered with 6-MV photons using a "sliding-window" technique. Enrollment of 6 patients for each dose level was planned; if DLTs were seen in >2 of 6 patients, the previous dose was to be expanded by an additional 6 patients to confirm that dose level as the MTD. All schedules administered a total of 30 fractions, but with escalating doses per fraction (2.27, 2.36, and 2.46 Gy) to achieve a total dose to the GTV of 68.1, 70.8, and 73.8 Gy, respectively. The remaining target tissues were constrained to receive the same dose in all patients regardless of the GTV dose level. The clinical target volume, defined as tissue within 1 cm around the GTV (at high risk of subclinical disease), received 60 Gy in 30 fractions of 2.0 Gy. The electively irradiated target volume, defined as the clinically uninvolved lymph node-bearing tissues, received 54 Gy in 30 fractions of 1.8 Gy. The parotid glands were spared to the degree possible without compromising target coverage. Acute toxicity was scored weekly using National Cancer Institute Common Toxicity Criteria. DLT was defined as any Grade 4 acute toxicity or any acute toxicity requiring either a dose reduction or a treatment break of >5 treatment days. RESULTS: Of 18 men and 2 women (average age, 57 years; range, 37-80 years), 17 presented with oropharyngeal primary tumors, and 1 each with squamous cell carcinoma of the oral cavity, nasopharynx, and hypopharynx. None of the 6 patients at dose level 1, and 2 of the 6 patients initially enrolled at dose level 2, developed DLT. Both patients treated at dose level 3 required a 3-day treatment break and dose reduction after rapid development of Grade 3 toxicity (by Day 15). Six additional confirmatory patients subsequently enrolled at dose level 2 completed treatment without DLT. At least 50% of the total parotid gland volume received <30 Gy in 14 patients (average, 54% of volume), with an average mean dose of 32 Gy. In contrast, >/=50% of the distal parotid gland volume received <25 Gy in 15 patients (average, 63% of volume), with an average mean dose of 24 Gy. With a median follow-up of 20 months from the date of enrollment and 28 months for surviving patients, the actuarial 2-year local control (primary site), regional control (nodal sites), and distant control rate was 76.3%, 66.7%, and 71.8%, respectively. CONCLUSION: Dose level 2, 70.8 Gy in 30 fractions of 2.36 Gy, was defined as the MTD deliverable to the GTV using this accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole treatment for locally advanced head-and-neck squamous cell carcinoma. Adequate parotid sparing was achievable in most cases. Early toxicity, tumor control, and survival rates compared favorably with the outcomes after other accelerated regimens.

Adult↗

PubMed2004

Cluster models of dose-volume effects.

PURPOSE: Describe cluster models, normal-tissue complication probability models in which both the number and the spatial location of radiation-sterilized functional subunits play a role in defining complication probability. METHODS AND MATERIALS: Computer simulation was used to determine the maximum size cluster of sterilized subunits associated with a given dose distribution. Complications were associated with large clusters. RESULTS: Cluster models showed a volume effect, as increasing effect for constant dose when the volume increased or constant effect when the dose was reduced with increasing volume. Cluster models gave similar results to existing models when tissues were irradiated uniformly. With inhomogeneous dose distributions, on the other hand, different spatial distributions of "hot spots" may lead to different predictions of complication probability by cluster models. The result was that a higher complication probability resulted when hot spots were contiguous (clustered) than when they were dispersed, even if both situations are characterized by the same dose-volume histogram. A potential advantage of cluster models is to provide an easy, internally consistent way to predict complications arising from the inhomogeneous dose distributions that sometimes arise with intensity-modulated radiotherapy. CONCLUSION: Cluster models offer a new way to quantify complication probability in treatment situations in which a wide variety of hot-spot distributions occur.

Animals↗

PubMed2004

Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system.

PURPOSE: Many patients receiving fractionated radiotherapy (RT) for head-and-neck cancer have marked anatomic changes during their course of treatment, including shrinking of the primary tumor or nodal masses, resolving postoperative changes/edema, and changes in overall body habitus/weight loss. We conducted a pilot study to quantify the magnitude of these anatomic changes with systematic CT imaging. METHODS AND MATERIALS: Fourteen assessable patients were enrolled in this pilot study. Eligible patients had to have a pathologic diagnosis of head-and-neck cancer, be treated with definitive external beam RT, and had have gross primary and/or cervical nodal disease measuring at least 4 cm in maximal diameter. All patients were treated using a new commercial integrated CT-linear accelerator system (EXaCT) that allows CT imaging at the daily RT sessions while the patient remains immobilized in the treatment position. CT scans were acquired three times weekly during the entire course of RT, and both gross tumor volumes (GTVs: primary tumor and involved lymph nodes) and normal tissues (parotid glands, spinal canal, mandible, and external contour) were manually contoured on every axial slice. Volumetric and positional changes relative to a central bony reference (the center of mass of the C2 vertebral body) were determined for each structure. RESULTS: Gross tumor volumes decreased throughout the course of fractionated RT, at a median rate of 0.2 cm(3) per treatment day (range, 0.01-1.95 cm(3)/d). In terms of the percentage of the initial volume, the GTVs decreased at a median rate of 1.8%/treatment day (range, 0.2-3.1%/d). On the last day of treatment, this corresponded to a median total relative loss of 69.5% of the initial GTV (range, 9.9-91.9%). In addition, the center of the mass of shrinking tumors changed position with time, indicating that GTV loss was frequently asymmetric. At treatment completion, the median center of the mass displacement (after corrections for daily setup variation) was 3.3 mm (range, 0-17.3 mm). Parotid glands also decreased in volume (median, 0.19 cm(3)/d range, 0.04-0.84 cm(3)/d), and generally shifted medially (median, 3.1 mm; range, 0-9.9 mm) with time. This medial displacement of the parotid glands correlated highly with the weight loss that occurred during treatment. CONCLUSION: Measurable anatomic changes occurred throughout fractionated external beam RT for head-and-neck cancers. These changes in the external contour, shape, and location of the target and critical structures appeared to be significant during the second half of treatment (after 3-4 weeks of treatment) and could have potential dosimetric impact when highly conformal treatment techniques are used. These data may, therefore, be useful in the development of an adaptive RT scheme (periodic adjustment of the conformal treatment plan) that takes into account such treatment-related anatomic changes. In theory, such a strategy would maximize the therapeutic ratio of RT.

Adult↗

PubMed2004

Dose-volume response analyses of late rectal bleeding after radiotherapy for prostate cancer.

PURPOSE: To compare the fits of various normal tissue complication probability (NTCP) models to a common set of late rectal toxicity data, with the aim of identifying the best model for predicting late rectal injury after irradiation. METHODS AND MATERIALS: Late toxicity data from 128 prostate cancer patients treated on protocol with three-dimensional conformal radiotherapy at The University of Texas M.D. Anderson Cancer Center (UTMDACC) were analyzed. The dose-volume histogram for total rectal volume, including contents, was obtained for each patient, and the presence or absence of Grade 2 or worse rectal bleeding within 2 years of treatment was scored. Five different NTCP models were fitted to the data using maximum likelihood analysis: the Lyman model, the mean dose model, a parallel architecture model, and models based on either a cutoff dose or a cutoff volume. RESULTS: All five of the NTCP models considered provided very similar fits to the UTMDACC rectal bleeding data. In particular, none of the more highly parameterized models (the four-parameter parallel model, three-parameter Lyman model, or three-parameter cutoff dose and volume models) provided a better fit than the simplest of the models, the two-parameter NTCP model describing rectal bleeding as a probit function of mean dose to rectum. CONCLUSION: No dose-volume response model has yet been identified that provides a better description of the UTMDACC rectal toxicity data than the mean dose model. Because this model has relatively low predictive accuracy, the need to identify a better model remains.

Dose-Response Relationship, Radiation↗

PubMed2004

Characterization of rectal normal tissue complication probability after high-dose external beam radiotherapy for prostate cancer.

PURPOSE: Conformal radiotherapy (RT) has allowed radiation dose escalation to improve the outcome of prostate cancer. With higher doses, concern exists that rectal injury may increase. This study analyzed the utility and limitations of the widely used Lyman-Kutcher- Burman (LKB) normal tissue complication probability model in projecting the hazards of rectal complication with high-dose RT. METHODS AND MATERIALS: A total of 128 patients were included in this study. These patients were treated with three-dimensional conformal RT alone at the University of Texas M.D. Anderson Cancer Center between 1992 and 1999. Patients were treated to 46 Gy with a four-field box technique followed by a six-field arrangement to boost the total dose to 78 Gy. All doses were delivered at 2 Gy/fraction to the isocenter. The minimal follow-up was 2 years. The end point for analysis was Grade 2 or worse rectal bleeding by 2 years. The LKB model was fitted to the data using the maximal likelihood method. RESULTS: Of the 128 patients, 29 experienced Grade 2 or worse rectal bleeding by 2 years. For the entire cohort, the parameters obtained from the fit of the LKB model were as follows: the volume factor was n = 3.91 (95% confidence interval [CI] 0.031 to infinity ), dose associated with 50% chance of complication for uniform whole rectal irradiation [TD50(1)] was 53.6 Gy (95% CI 50.0-75.1), and a determinant of the steepness of the dose-response curve, (m), was 0.156 (95% CI 0.036-0.271). A statistically significant difference was found in the rate of postradiation rectal bleeding in patients with hemorrhoids vs. those without hemorrhoids. The parameters obtained for the patients without hemorrhoids were as follows: n = 0.746 (95% CI 0.026 to infinity ), TD50(1) 56.7 Gy (95% CI 49.9-75.2), and m 0.092 (95% CI 0.019-0.189). CONCLUSION: Our analysis suggests a dose response for rectal bleeding probability along with a volume effect. We found that the LKB model might have limited utility in determining a large volume effect. We further suggest that LKB model should be used with caution in clinical practice.

Dose-Response Relationship, Radiation↗

PubMed2004

Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer.

PURPOSE: To investigate the possibility of using intensity-modulated radiotherapy (IMRT) to reduce the irradiated volumes of the normal lung and other critical structures in the treatment of non-small-cell lung cancer (NSCLC) and to investigate the effect of IMRT on the potential of spreading low doses to large volumes of normal tissues in such treatment. METHODS AND MATERIALS: A retrospective treatment planning study was performed to compare IMRT and conventional three-dimensional conformal radiation therapy (3D-CRT) for 10 NSCLC patients (Stage I-IIIB). In the IMRT plans, three to nine coplanar beams were designed to treat 95% of the planning target volume with 63 Gy and to minimize the volumes of the normal lung, esophagus, heart, and spinal cord irradiated above their tolerance doses. The two types of plans were compared with respect to the planning target volume coverage, dose-volume histograms, and other dosimetric indexes of the normal structures. RESULTS: Comparing the nine-beam IMRT plan with the 3D-CRT plan, the percentage of lung volume that received >20 Gy and the mean lung dose were reduced for all cases, with a median reduction of 8% and 2 Gy, respectively. An additional reduction of the >5-Gy volume and >10-Gy volume for the lung and thoracic tissue was more difficult with IMRT, although still possible using fewer beams in IMRT. The integral dose to the entire thorax was equivalent and even reduced for 8 of 10 cases using IMRT. CONCLUSION: It is possible to reduce the volumes of low doses (such as the >10-Gy volume and >20-Gy volume) for thoracic normal tissues using IMRT. The increased integral dose and low-dose volumes can be avoided for IMRT if such concerns are addressed carefully in the inverse planning process and with optimization of the IMRT beam configuration.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer.

PURPOSE: To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared. RESULTS: Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40-50 Gy and normal thoracic tissue volume irradiated to >10-40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT. CONCLUSION: IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.

Adult↗

PubMed2004

Speed and convergence properties of gradient algorithms for optimization of IMRT.

Gradient algorithms are the most commonly employed search methods in the routine optimization of IMRT plans. It is well known that local minima can exist for dose-volume-based and biology-based objective functions. The purpose of this paper is to compare the relative speed of different gradient algorithms, to investigate the strategies for accelerating the optimization process, to assess the validity of these strategies, and to study the convergence properties of these algorithms for dose-volume and biological objective functions. With these aims in mind, we implemented Newton's, conjugate gradient (CG), and the steepest decent (SD) algorithms for dose-volume- and EUD-based objective functions. Our implementation of Newton's algorithm approximates the second derivative matrix (Hessian) by its diagonal. The standard SD algorithm and the CG algorithm with "line minimization" were also implemented. In addition, we investigated the use of a variation of the CG algorithm, called the "scaled conjugate gradient" (SCG) algorithm. To accelerate the optimization process, we investigated the validity of the use of a "hybrid optimization" strategy, in which approximations to calculated dose distributions are used during most of the iterations. Published studies have indicated that getting trapped in local minima is not a significant problem. To investigate this issue further, we first obtained, by trial and error, and starting with uniform intensity distributions, the parameters of the dose-volume- or EUD-based objective functions which produced IMRT plans that satisfied the clinical requirements. Using the resulting optimized intensity distributions as the initial guess, we investigated the possibility of getting trapped in a local minimum. For most of the results presented, we used a lung cancer case. To illustrate the generality of our methods, the results for a prostate case are also presented. For both dose-volume and EUD based objective functions, Newton's method far outperforms other algorithms in terms of speed. The SCG algorithm, which avoids expensive "line minimization," can speed up the standard CG algorithm by at least a factor of 2. For the same initial conditions, all algorithms converge essentially to the same plan. However, we demonstrate that for any of the algorithms studied, starting with previously optimized intensity distributions as the initial guess but for different objective function parameters, the solution frequently gets trapped in local minima. We found that the initial intensity distribution obtained from IMRT optimization utilizing objective function parameters, which favor a specific anatomic structure, would lead to a local minimum corresponding to that structure. Our results indicate that from among the gradient algorithms tested, Newton's method appears to be the fastest by far. Different gradient algorithms have the same convergence properties for dose-volume- and EUD-based objective functions. The hybrid dose calculation strategy is valid and can significantly accelerate the optimization process. The degree of acceleration achieved depends on the type of optimization problem being addressed (e.g., IMRT optimization, intensity modulated beam configuration optimization, or objective function parameter optimization). Under special conditions, gradient algorithms will get trapped in local minima, and reoptimization, starting with the results of previous optimization, will lead to solutions that are generally not significantly different from the local minimum.

Algorithms↗

PubMed2004

Monte Carlo computation of dosimetric amorphous silicon electronic portal images.

This study develops and tests a method to compute dosimetric images for an amorphous silicon (a-Si) flat-panel detector so that an accurate quantitative comparison between measured and computed portal images may be made. An EGS4-based Monte Carlo (MC) algorithm is developed to efficiently tally the energy deposition through the use of a virtual detector dose-scoring methodology. The complete geometry of the a-Si imager is utilized in the MC calculation up to the imager rear housing, which is replaced with a uniform thickness material slab. The detector-mounting hardware is modeled as a uniform backscattering material. The amount of backscatter material required to reproduce the measured backscatter is 0.98 g/cm2 of water. A flood-field irradiation, performed in the measurement imaging session, is used to cross-calibrate the computed images with the measured images. Calibrated MC-computed images reproduce measured field-size dependencies of the electronic portal imaging device (EPID) response to within <1%, without the need for optical glare or other empirical corrections. A 10% dose difference between measured and computed images was observed outside the field edge for a 10 x 10 cm2 field that was entirely blocked by the multileaf collimator (MLC). However, this error corresponded with less than 0.15% of the open-field dose. For 10 x 10 cm2 fields produced by 5 and 20 mm dynamically sweeping MLC gaps, more than 98% of the points were found to have a gamma less than one with a 2%, 2 mm criteria. For an intensity modulated radiation therapy (IMRT) patient test field, over 99% of the points were found to have a gamma less than one with a 2%, 2 mm criteria. This study demonstrates that MC can be an effective tool for predicting measured a-Si portal images and may be useful for IMRT EPID-based dosimetry.

Algorithms↗

PubMed2003

Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram parameters.

PURPOSE: To clarify the relationship between the percentage of lung receiving low radiation doses with concurrent chemotherapy and the occurrence of postoperative pulmonary complications in the treatment of esophageal carcinoma. METHODS: From 117 patients who underwent preoperative chemoradiation for esophageal cancer at our institution between 1998 and 2002, we selected 61 patients for whom complete pulmonary dose-volume histogram (DVH) data were available and analyzed the incidence of pneumonia and acute respiratory distress syndrome (ARDS) in this group. All patients received concurrent chemoradiation therapy, and 39 patients also received induction chemotherapy before concurrent chemoradiation. The median age was 62 years, and the median radiotherapy dose was 45 Gy. The percentage of lung volume receiving at least 10 Gy (V10), 15 Gy (V15), and 20 Gy (V20) were recorded from each pulmonary DVH. RESULTS: Eleven (18%) of the 61 patients had pulmonary complications, 2 of whom died after progression of pneumonia. Pulmonary complications were noted more often (35% vs. 8%, p = 0.014) when the pulmonary V10 was > or =40% vs. <40% and when the V15 was > or /=30% vs. < 30% (33% vs. 10%, p = 0.036). An apparent increase in pulmonary complication rate when V20 was > or =20% vs. <20% (32% vs. 10%, p = 0.079) was not significant. None of the other factors analyzed (surgical procedure, tumor location, use of induction chemotherapy, use of concurrent taxane-based chemoradiation, or smoking history) was associated with the occurrence of pulmonary complications. The median hospital stay was 17 days for patients who had pulmonary complications vs. 12 days for patients who did not (p = 0.08). CONCLUSIONS: The use of multimodality therapy may require minimization of lung volume irradiation to levels lower than previously expected. Radiotherapy techniques that decrease the volume of lung receiving low radiation doses may significantly reduce the risk of this potentially life-threatening complication.

Adenocarcinoma↗

PubMed2003

Near simultaneous computed tomography image-guided stereotactic spinal radiotherapy: an emerging paradigm for achieving true stereotaxy.

PURPOSE: To report treatment setup data from an emerging technique using near-simultaneous computed tomography (CT) image-guided stereotactic radiotherapy for the treatment of spinal and paraspinal tumors. METHODS AND MATERIALS: A targeting system that integrates a CT-on-rails scanner with a linear accelerator (LINAC) was evaluated in the lead-in portion of a Phase I/II protocol for treating patients with paraspinal metastases. Patients were immobilized in supine position by a moldable body cushion vacuum wrapped with a plastic fixation sheet. Planning CT and immediately repeated CT were performed on the LINAC/CT-on-rails unit to assess respiratory-related vertebral body motion. Coplanar intensity-modulated radiotherapy (IMRT) using 7-9 beams was used to deliver 30 Gy in five fractions to the target volume, while limiting the spinal cord dose to <10 Gy. Pretreatment CT scans were fused with the planning CT scans to determine the correct target isocenter by accounting for any translational and roll (axial) rotational discrepancies from the planning CT. (Corrections caused by yaw and pitch rotations have not yet been implemented.) The reproducibility of the treatment isocenter as compared with the planned isocenter was measured with digitally reconstructed radiographs (DRRs), portal film imaging, and immediate post-treatment verification CT scans. Phantom measurements were taken for dose verification for each IMRT plan. RESULTS: Based on a total of 36 CT scans (3 for planning, 3 for respiration study, 15 pretreatment, and 15 post-treatment) from 3 patients, no respiration-associated vertebral body motion was seen. A comparison of the corrected daily anterior-posterior (AP) and lateral (LAT) digital portal images with the planning AP and LAT DRRs confirmed that the isocenter setup accuracy for the 15 treatments was within 1 mm of the planning isocenter. The results from the immediate post-treatment CT scans reconfirmed the findings from the portal images and verified the absence of spinal movement during the treatment. The ion-chamber measurement for the high-dose region was within 2% of the planning dose for three patient treatment plans. Film dose measurement in an IMRT quality assurance phantom demonstrated good agreement from 90% to 30% isodose lines between the planned and measured results. CONCLUSION: Preliminary experience suggests that the near-simultaneous CT image-guided verification technique can be used as a new platform technology for extracranial applications of stereotactic radiotherapy and radiosurgery to spinal and paraspinal tumors.

Equipment Design↗

PubMed2003

Algorithm and performance of a clinical IMRT beam-angle optimization system.

This paper describes the algorithm and examines the performance of an intensity-modulated radiation therapy (IMRT) beam-angle optimization (BAO) system. In this algorithm successive sets of beam angles are selected from a set of predefined directions using a fast simulated annealing (FSA) algorithm. An IMRT beam-profile optimization is performed on each generated set of beams. The IMRT optimization is accelerated by using a fast dose calculation method that utilizes a precomputed dose kernel. A compact kernel is constructed for each of the predefined beams prior to starting the FSA algorithm. The IMRT optimizations during the BAO are then performed using these kernels in a fast dose calculation engine. This technique allows the IMRT optimization to be performed more than two orders of magnitude faster than a similar optimization that uses a convolution dose calculation engine. Any type of optimization criterion present in the IMRT system can be used in this BAO system. An objective function based on clinically-relevant dose-volume (DV) criteria is used in this study. This facilitates the comparison between a BAO plan and the corresponding plan produced by a planner since the latter is usually optimized using a DV-based objective function. A simple prostate case and a complex head-and-neck (HN) case were used to evaluate the usefulness and performance of this BAO method. For the prostate case we compared the BAO results for three, five and seven coplanar beams with those of the same number of equispaced coplanar beams. For the HN case we compare the BAO results for seven and nine non-coplanar beams with that for nine equispaced coplanar beams. In each case the BAO algorithm was allowed to search up to 1000 different sets of beams. The BAO for the prostate cases were finished in about 1-2 h on a moderate 400 MHz workstation while that for the head-and-neck cases were completed in 13-17 h on a 750 MHz machine. No a priori beam-selection criteria have been used in achieving this performance. In both the prostate and the head-and-neck cases, BAO is shown to provide improvements in plan quality over that of the equispaced beams. The use of DV-based objective function also allows us to study the dependence of the improvement of plan quality offered by BAO on the DV criteria used in the optimization. We found that BAO is especially useful for cases that require strong DV criteria. The main advantages of this BAO system are its speed and its direct link to a clinical IMRT system.

Algorithms↗

PubMed2003

Tumor control probability predictions for genetic radiotherapy.

PURPOSE: Genetic radiotherapy, the combination of gene therapy and radiation therapy, for cancer treatment is evolving from laboratory studies to clinical trials. Genetic radiotherapy involves the viral infection of cells that change the sensitivity of transduced cells to radiation. Because there is no patient outcome data for genetic radiotherapy, prospective models are needed to determine the expected benefit of this new modality. Such a prospective model has been developed in this work. METHODS AND MATERIALS: An existing tumor control probability (TCP) calculation model developed for external beam radiotherapy was modified for genetic radiotherapy. Specifically, the (1) transduced fraction and (2) enhancement factor of the transduced cells were included in the model. Parametric studies of the effects of these two variables on TCP for head-and-neck cancer were performed. RESULTS: Using reasonable transduction fraction and enhancement factor values (0.8 and 1.4, respectively), the model predicts an increase in the TCP for genetic radiotherapy over radiotherapy alone by up to 15% for the same radiotherapy dose. The theoretical limit of TCP increase was calculated to be near 70%, which may occur with improved techniques that increase the transduced fraction or because of a strong bystander effect. To maintain existing TCP, dose reductions from 5 Gy (reasonable values) to >30 Gy (ideal case) are predicted for genetic radiotherapy over radiotherapy alone. CONCLUSIONS: Our results indicate that genetic radiotherapy has the potential to significantly improve tumor control over radiotherapy alone.

Combined Modality Therapy↗

PubMed2003

A fast dose calculation method based on table lookup for IMRT optimization.

This note describes a fast dose calculation method that can be used to speed up the optimization process in intensity-modulated radiotherapy (IMRT). Most iterative optimization algorithms in IMRT require a large number of dose calculations to achieve convergence and therefore the total amount of time needed for the IMRT planning can be substantially reduced by using a faster dose calculation method. The method that is described in this note relies on an accurate dose calculation engine that is used to calculate an approximate dose kernel for each beam used in the treatment plan. Once the kernel is computed and saved, subsequent dose calculations can be done rapidly by looking up this kernel. Inaccuracies due to the approximate nature of the kernel in this method can be reduced by performing scheduled kernel updates. This fast dose calculation method can be performed more than two orders of magnitude faster than the typical superposition/convolution methods and therefore is suitable for applications in which speed is critical, e.g., in an IMRT optimization that requires a simulated annealing optimization algorithm or in a practical IMRT beam-angle optimization system.

Algorithms↗

PubMed2003

Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas. I: dosimetric results.

PURPOSE: This report describes the dosimetric analyses of a Phase I/II protocol, designed to examine the capabilities of an institutionally developed intensity-modulated radiotherapy (IMRT) system with respect to dose escalation. The protocol employed stringent dosimetric guidelines in the treatment of locally advanced head-and-neck squamous cell carcinomas (HNSCC) with radiotherapy alone using IMRT and the simultaneous integrated boost (SIB) technique. METHODS AND MATERIALS: The first 14 patients enrolled on the protocol were included in this analysis. Escalating doses of 68.1 Gy (6 patients), 70.8 Gy (6 patients), and 73.8 Gy (2 patients) were delivered to the gross tumor volume (GTV) in 30 fractions. Simultaneously, constant dose coverage was given to the subclinical disease and the electively treated nodal regions, which received 60 Gy and 54 Gy, respectively, in all three cohorts. Parotid glands were spared to the degree possible without compromising target coverage. The following indices are reported for the GTV: (1) dose to specified percent volumes (e.g., D(98) and D(2)); (2) homogeneity index defined as the ratio (D(2) - D(98))/D(prescription); (3) biologically equivalent uniform dose (EUD); and (4) an index of conformality, PITV, defined as the ratio of volume enclosed within the prescribed isodose surface to the target volume. Treatments were planned and delivered with nine 6-MV photon beams using the multileaf collimator (MLC) "sliding window" technique. RESULTS: Mean doses to 98% of GTV were 68.4 Gy, 70.5 Gy, and 70.8 Gy, and average GTV dose homogeneity was 6.7%, 7.6%, and 8.8% for the three cohorts. The average doses to the parotid gland proximal to and distant from GTV were 41.3 Gy and 25.7 Gy, respectively. Dose distributions measured in phantom showed good agreement with calculations. CONCLUSIONS: Treatment of locally advanced HNSCC using SIB-IMRT as described is feasible. Treatment planning and delivery are safer and more efficient than with conventional three-dimensional processes. Predicted dose distributions can be accurately delivered with excellent conformality using dynamic MLC. At least one of the parotid glands can be adequately spared. Patient follow-up continues and will allow eventual quantitative correlation of delivered dose distributions with clinical outcomes.

Carcinoma, Squamous Cell↗

PubMed2003

Intensity-modulated radiotherapy optimization with gEUD-guided dose-volume objectives.

Currently, most intensity-modulated radiation therapy systems use dose-volume (DV)-based objectives. Although acceptable plans can be generated using these objectives, much trial and error is necessary to plan complex cases with many structures because numerous parameters need to be adjusted. An objective function that makes use of a generalized equivalent uniform dose (gEUD) was developed recently that has the advantage of involving simple formulae and fewer parameters. In addition, not only does the gEUD-based optimization provide the same coverage of the target, it provides significantly better protection of critical structures. However, gEUD-based optimization may not be superior once dose distributions and dose-volume histograms (DVHs) are used to evaluate the plan. Moreover, it is difficult to fine-tune the DVH with gEUD-based optimization. In this paper, we propose a method for combining the gEUD-based and DV-based optimization approaches to overcome these limitations. In this method, the gEUD optimization is performed initially to search for a solution that meets or exceeds most of the treatment objectives. Depending on the requirements, DV-based optimization with a gradient technique is then used to fine-tune the DVHs. The DV constraints are specified according to the gEUD plan, and the initial intensities are obtained from the gEUD plan as well. We demonstrated this technique in two clinical cases: aprostate cancer and ahead and neck cancer case. Compared with the DV-optimized plan, the gEUD plan provided better protection of critical structures and the target coverage was similar. However, homogeneities were slightly poorer. The gEUD plan was then fine-tuned with DV constraints, and the resulting plan was superior to the other plans in terms of the dose distributions. The planning time was significantly reduced as well. This technique is an effective means of optimizing individualized treatment plans.

Adenocarcinoma↗

PubMed2003

Patient training in respiratory-gated radiotherapy.

Respiratory gating is used to counter the effects of organ motion during radiotherapy for chest tumors. The effects of variations in patient breathing patterns during a single treatment and from day to day are unknown. We evaluated the feasibility of using patient training tools and their effect on the breathing cycle regularity and reproducibility during respiratory-gated radiotherapy. To monitor respiratory patterns, we used a component of a commercially available respiratory-gated radiotherapy system (Real Time Position Management (RPM) System, Varian Oncology Systems, Palo Alto, CA 94304). This passive marker video tracking system consists of reflective markers placed on the patient's chest or abdomen, which are detected by a wall-mounted video camera. Software installed on a PC interfaced to this camera detects the marker motion digitally and records it. The marker position as a function of time serves as the motion signal that may be used to trigger imaging or treatment. The training tools used were audio prompting and visual feedback, with free breathing as a control. The audio prompting method used instructions to "breathe in" or "breathe out" at periodic intervals deduced from patients' own breathing patterns. In the visual feedback method, patients were shown a real-time trace of their abdominal wall motion due to breathing. Using this, they were asked to maintain a constant amplitude of motion. Motion traces of the abdominal wall were recorded for each patient for various maneuvers. Free breathing showed a variable amplitude and frequency. Audio prompting resulted in a reproducible frequency; however, the variability and the magnitude of amplitude increased. Visual feedback gave a better control over the amplitude but showed minor variations in frequency. We concluded that training improves the reproducibility of amplitude and frequency of patient breathing cycles. This may increase the accuracy of respiratory-gated radiation therapy.

Acoustic Stimulation↗

PubMed2003

Radiotherapy dose calculations in the presence of hip prostheses.

The high density and atomic number of hip prostheses for patients undergoing pelvic radiotherapy challenge our ability to accurately calculate dose. A new clinical dose calculation algorithm, Monte Carlo, will allow accurate calculation of the radiation transport both within and beyond hip prostheses. The aim of this research was to investigate, for both phantom and patient geometries, the capability of various dose calculation algorithms to yield accurate treatment plans. Dose distributions in phantom and patient geometries with high atomic number prostheses were calculated using Monte Carlo, superposition, pencil beam, and no-heterogeneity correction algorithms. The phantom dose distributions were analyzed by depth dose and dose profile curves. The patient dose distributions were analyzed by isodose curves, dose-volume histograms (DVHs) and tumor control probability/normal tissue complication probability (TCP/NTCP) calculations. Monte Carlo calculations predicted the dose enhancement and reduction at the proximal and distal prosthesis interfaces respectively, whereas superposition and pencil beam calculations did not. However, further from the prosthesis, the differences between the dose calculation algorithms diminished. Treatment plans calculated with superposition showed similar isodose curves, DVHs, and TCP/NTCP as the Monte Carlo plans, except in the bladder, where Monte Carlo predicted a slightly lower dose. Treatment plans calculated with either the pencil beam method or with no heterogeneity correction differed significantly from the Monte Carlo plans.

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