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Biomedical subjects

George Starkschall

Publications and source records attributed to George Starkschall.

27 records · Page 2Linked to original sources

The relationship between local dose and loss of function for irradiated lung.

PURPOSE: To determine the relationship between the local radiation dose and the decrease in lung function associated with thoracic irradiation. PATIENTS AND METHODS: Twenty-six patients treated with thoracic irradiation for lung cancer, for whom three-dimensional CT-based dosimetry was used in treatment planning, were evaluated with before and after treatment pulmonary function tests. Six patients were treated with radiotherapy alone (2.15 Gy daily fractions), and 20 patients with concurrent chemotherapy (cisplatin, etoposide) with hyperfractionated (HF) radiation therapy (1.2 Gy in twice-daily fractions). Eleven patients treated with concurrent HF chemoradiation also received the radioprotector amifostine. The normalized decrease in the diffusing capacity for carbon monoxide (DL(CO)) was used as an objective measure of the change in lung function. The dose-volume histogram (DVH) data were used to estimate the local dose-response relationship for loss of DL(CO). In each subvolume of lung, the loss in normalized DL(CO) was assumed to be a sigmoid function of dose, ranging from no loss at low doses to total loss at high doses. The whole-lung decrease in DL(CO) was modeled as the sum of the local declines in DL(CO) over all subvolumes. Nonlinear regression analysis was used to estimate the parameters of the local dose-response function. RESULTS: The data are most consistent with a pronounced decrease in DL(CO) when the local dose (for radiotherapy alone or HF concurrent chemoradiation) exceeds 13 Gy (95% CI, 11-15 Gy). In patients who received amifostine in addition to HF radiotherapy with concurrent chemotherapy, this stepwise loss of DL(CO) occurred above 36 Gy (95% CI, 25-48 Gy). Grade 2 or higher pulmonary symptoms were associated with a DL(CO) loss of >30% (p = 0.003). CONCLUSIONS: The decrease in pulmonary diffusion capacity correlates with the local dose to irradiated lung. Amifostine significantly reduces the loss in DL(CO). A local dose-loss relationship for normalized DL(CO) can be extracted from DVH data. This relationship allows an estimate of the loss of function associated with a radiation treatment plan. Different plans can thus be compared without resort to an empiric DVH reduction algorithm. The very low (13 Gy) threshold for deterioration of DL(CO) suggests that it is better to treat a little normal lung to a high dose than to treat a lot to a low dose.

Adult↗

Intensity-modulated radiotherapy following extrapleural pneumonectomy for the treatment of malignant mesothelioma: clinical implementation.

PURPOSE: New insight into the extent of the target volume for the postoperative irradiation of malignant pleural mesothelioma as determined during surgery has indicated that standard conformal radiotherapy (IMRT) is not sufficient for curative treatment. We describe a novel technique for implementing intensity-modulated radiotherapy (IMRT) to deliver higher doses to treat the full extent of these complex target volumes. METHODS AND MATERIALS: After extrapleural pneumonectomy, 7 patients underwent simulation, treatment planning, and treatment with IMRT to the involved hemithorax and adjacent abdomen. The target volumes encompassed the entire operative bed, including the ipsilateral mediastinum, anterior pleural reflection, and ipsilateral pericardium and the insertion of the diaphragm and crura. These were extensively marked during surgery with radiopaque markers to facilitate target delineation. RESULTS: Setup uncertainty and respiratory-dependent motion were found to be small. Coverage of the planning target volume was very good, with the crus of the diaphragm the most difficult volume to irradiate. The radiation doses to normal structures were acceptable. CONCLUSION: IMRT for treatment of malignant mesothelioma after extrapleural pneumonectomy results in more potentially curative doses to large, complex target volumes with acceptable doses to normal tissues.

Humans↗

Intensity-modulated radiation therapy: a novel approach to the management of malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) causes symptoms and death mainly due to local progression, even after combined modality treatment. Poor local control after conventional radiotherapy may be due to the low dose of radiation that has been administered or to restriction of the target volume to avoid critical organs. Intensity-modulated radiation therapy (IMRT) has the potential to overcome these geometric/dosimetric constraints. METHODS AND MATERIALS: Seven patients with MPM who had an extrapleural pneumonectomy (EPP) were treated with adjuvant IMRT. The clinical target volume (CTV) included the surgically violated area inside the chest wall with particular attention to the insertion of the diaphragm, pleural reflections, and the deep margin of the thoracotomy incision. Treatment was delivered by intensity-modulated 6-MV photon beams using dynamic multileaf collimation. RESULTS: The CTV ranged from 2667 to 7286 mL. The average CTV covered to 50 Gy was 94% (range, 92% to 98%). Respiratory motion was minimal. The average volume of the boost areas covered by 60 Gy was 92% (range, 82% to 99%). Dose-volume constraints for normal tissue were met in almost all cases. Acute toxicity was mild to moderate. The most severe side effects were anorexia, nausea or vomiting, and dyspnea. Esophagitis was absent or mild. After a minimum of 13 months follow-up care there were no cases of disease recurrence within the ipsilateral hemithorax. CONCLUSION: Treatment of the extensive operative area after an EPP is feasible using IMRT. Input from the radiologist and from the surgeon in the planning process facilitates definition of the high dose volumes. In light of patients' tolerance to post-EPP IMRT, it may be feasible to incorporate systemic therapy, including novel biologic therapies into the treatment regimen.

Aged↗

Assessment of consistency in contouring of normal-tissue anatomic structures.

The purpose of this work is to estimate the uncertainty in the manual contouring of normal anatomical structures. The heart, esophagus, and spinal cord were contoured manually on six sets of computed tomography images by six dosimetrists whose experience ranged from 1 year to over 15 years. To determine the differences between inter- and intraobserver variations, each data set was contoured by one of the dosimetrists five times and once each by the five other dosimetrists. The magnitude of the discrepancies in delineating the contours was assessed. Intradosimetrist contouring discrepancies were as follows: esophagus, average 0.3 cm and maximum 2.9 cm; heart, average 0.5 cm and maximum 7.6 cm; and spinal cord, average 0.1 cm and maximum 0.7 cm. Interdosimetrist contouring discrepancies were as follows: esophagus, average 0.4 cm and maximum 3.1 cm; heart, average 0.7 cm and maximum 8.1 cm; and spinal cord, average 0.2 cm and maximum 0.9 cm. Significant discrepancies can occur when normal anatomic structures are contoured manually. Interdosimetrist discrepancies are typically slightly greater than intradosimetrist discrepancies. The magnitude of the discrepancies does not appear to be correlated to the experience of the dosimetrist.

Esophagus↗

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↗

Plan space: representation of treatment plans in multidimensional space.

PURPOSE: Treatment planning balances the need to provide adequate radiation coverage of the target with the need to reduce against the risk of overdosing normal tissues. An acceptable plan fulfills minimum dose-volume criteria for irradiation of tumor and normal tissues. However, multiple plans can satisfy these minimum criteria, and some plans provide for better protection of normal tissue than others. Here, we present a method to help the planner compare plans and decide whether a particular plan is the "best" plan on the basis of a set of certain dose-volume conditions. METHODS AND MATERIALS: Treatment plans are represented as points in multidimensional space. One dimension is assigned to the target and one to normal tissues of each anatomic structure under consideration. Minimum target dose is used as the target axis coordinate and the percentage volume of each normal structure receiving more than a specified dose as each normal-tissue coordinate. Images of plan space are developed for model phantom anatomy as well as for two clinical cases in the thorax and abdomen. RESULTS: When a sufficient number of plans have been plotted, a feasibility boundary becomes evident. This hypersurface in plan space represents the limit of the given treatment technique. By using a plan on this boundary, the benefits of a given treatment modality are maximized, providing assurance that the selected plan is the "best" plan. The beam angles and relative weights of a plan can be changed to alter its position in plan space, allowing improvements in an existing plan. Frequently, plans with normal-tissue dose distributions superior to the minimum acceptable criteria can be selected. The benefits of using plan-space images have been demonstrated at sites in the thorax and abdomen. CONCLUSION: Instead of defining dose-volume criteria at the outset, it is possible to select the best achievable plans by first evaluating the space of possible plans for a particular patient's unique anatomy and then choosing the plan with the optimum dose-volume characteristics. No attempt is made to arrive at a single plan score so that explicit judgments about the relative worth of individual structures are avoided. Visualization of plan-space images allows physicians to make choices based on their assessment of the relative significance of irradiation of each normal structure.

Humans↗

The effect of titanium stabilization rods on spinal cord radiation dose.

The purpose of this study was to investigate the dosimetric effect of a titanium-rod spinal stabilization system on surrounding tissue, especially the spinal cord. Ion chamber dosimetry was performed for 6- and 18-MV photon beams in a water phantom containing a titanium-rod spinal stabilization system. Isodose curves were obtained in the phantom with and without rods. To assess the ability of a treatment planning system to reproduce the effects of the stabilization system on the radiation dose delivered to surrounding tissue, dose distributions were calculated after appropriate modifications were made in the computed tomography number-to-density conversion table to account for the increased density of the titanium rods. The resultant heterogeneity-corrected plans were compared with uncorrected plans. At a 7-cm depth in the water phantom, corresponding to the depth of the spinal cord, the beam was attenuated by 4% under the rods alone and by 13% rods under the rods with screws for the 6-MV photon beam as compared with curves generated in the absence of rods. The beam was attenuated by 3% and 11%, respectively, for the 18-MV beam. Using anteroposterior (18-MV) and posteroanterior (6-MV) photon beams, with and without heterogeneity correction for the rods, the corrected isodose plan showed an approximately 2% beam attenuation 4 cm anterior to the rods as compared with the uncorrected plan. No significant difference in the spinal cord dose was observed between the 2 plans, however. The titanium-rod spinal stabilization system tested in this study caused a decrease in the dose delivered distal to the rods but did not significantly affect the dose delivered to the spinal cord.

Humans↗

Verification of the accuracy of a photon dose-calculation algorithm.

An extensive set of measured data was developed for the purpose of verifying the accuracy of a photon dose-calculation algorithm. Dose distributions from a linear accelerator were measured using an ion chamber in a water phantom and thermoluminescent dosimeters in a heterogeneous anthropomorphic phantom. Test cases included square fields, rectangular fields, fields having different source-to-surface distances, wedged fields, irregular fields, obliquely incident fields, asymmetrically collimated fields with wedges, multileaf collimator-shaped fields, and two heterogeneous density cases. The data set was used to validate the photon dose-calculation algorithm in a commercial radiation treatment planning system. The treatment planning system calculated photon doses to within the American Association of Physicists in Medicine (AAPM) Task Group 53 (TG-53) criteria for 99% of points in the buildup region, 90% of points in the inner region, 88% of points in the outer region, and 93% of points in the penumbra. For the heterogeneous phantoms, calculations agreed with actual measurements to within +/-3%. The monitor unit tests revealed that the 18-MV open square fields, oblique incidence, oblique incidence with wedge, and mantle field test cases did not meet the TG-53 criteria but were within +/-2.5% of measurements. It was concluded that (i) the photon dose calculation algorithm used by the treatment planning system did not meet the TG-53 criteria 100% of the time; (ii) some of the TG-53 criteria may need to be modified, and (iii) the generally stated goal of accuracy in dose delivery of within 5% cannot be met in all situations using this beam model in the treatment planning system.

Algorithms↗