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Biomedical subjects

Ellen D Yorke

Publications and source records attributed to Ellen D Yorke.

11 recordsLinked to original sources

The atlas of complication incidence: a proposal for a new standard for reporting the results of radiotherapy protocols.

We present a new method of reporting the results of radiotherapy protocols. The dose-volume atlas of complication incidence is a comprehensive and unbiased summary of the dose-volume exposures and complications occurring in patients after treatment. This new tool provides clear and systematic information about the safety of regions of dose-volume exposure previously treated that can be used when considering new treatments. Actuarial and model-dependent versions of the atlas are described. By using the raw data in the appropriate forms of the atlas, logistic regression, Kaplan-Meier, and Cox proportional hazards analysis can be performed, allowing for the independent calculation of dose-volume response. The data required are simple enough that provided compatible definitions of dose, volume, and complications are used, atlases from different protocols are potentially additive, facilitating the meta-analysis of inter-interinstitutional data. If this method were adopted as a standard for reporting the outcome of treatment protocols, a potentially synergistic increase in the utility of each protocol could result.

Clinical Protocols↗

Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study.

PURPOSE: To determine dosimetric factors for lung, lung subregions, and heart that correlate with radiation pneumonitis (Radiation Therapy Oncology Group Grade 3 or more) in the 78 evaluable patients from a Phase I dose escalation study (1991-2003) of three-dimensional conformal radiation therapy (3D-CRT) of non-small-cell lung cancer. METHODS AND MATERIALS: There were 10 > or = Grade 3 pneumonitis cases within 6 months after treatment. Dose-volume factors analyzed for univariate correlation with > or = Grade 3 pneumonitis were mean dose (MD), effective uniform dose (d(eff)), normal tissue complication probability (NTCP), parallel model f(dam) and V(D) for 5 < or = D < or = 60 Gy for whole, ipsilateral, contralateral, upper and lower halves of the lungs and heart D05, and mean and maximum doses. RESULTS: The most significant variables (0.005 < p < 0.006) were ipsilateral lung V(D) for D < 20 Gy. Also significant (p < 0.05) for ipsilateral lung were V(D) for D < 50 Gy, MD, f(dam) and d(eff); for total lung V(D) (D < 50 Gy), MD, f(dam), d(eff) and NTCP; for lower lung V(D) (D < 60 Gy), MD, f(dam) and d(eff). All variables for upper and contralateral lung were insignificant, as were heart variables. CONCLUSIONS: Previously reported correlations between severe pneumonitis and whole lung V13 and with other dose-volume factors of total lung and lower lung are confirmed. The most significant correlations were for (V05-V13) in ipsilateral lung.

Adult↗

Methodology for biologically-based treatment planning for combined low-dose-rate (permanent implant) and high-dose-rate (fractionated) treatment of prostate cancer.

PURPOSE: The combination of permanent low-dose-rate interstitial implantation (LDR-BRT) and external beam radiotherapy (EBRT) has been used in the treatment of clinically localized prostate cancer. While a high radiation dose is delivered to the prostate in this setting, the actual biologic dose equivalence compared to monotherapy is not commonly invoked. We describe methodology for obtaining the fused dosimetry of this combined treatment and assigning a dose equivalence which in turn can be used to develop desired normal tissue and target constraints for biologic-based treatment planning. METHODS AND MATERIALS: Patients treated with this regimen initially receive an I-125 implant prescribed to 110 Gy followed, 2 months later, by 50.4 Gy in 28 fractions using intensity-modulated external beam radiotherapy. Ab initio methodology is described, using clinically derived biologic parameters (alpha, beta, potential doubling time for prostate cancer cells [T(pot)], cell loss factor), for calculating tumor control probability isoeffective doses for the combined LDR and conventional fraction EBRT treatment regimen. As no such formalism exists for assessing rectal or urethral toxicity, we make use of semi-empirical expressions proposed for describing urethral and rectal complication probabilities for specific treatment situations (LDR and fractionation, respectively) and utilize the notion of isoeffective dose to extend these results to combined LDR-EBRT regimens. RESULTS: The application to treatment planning of the methodology described in this study is illustrated with real-patient data. We evaluate the effect of changing LDR and EBRT prescription doses (in a manner that remains isoeffective with 81 Gy EBRT alone or with 144 Gy LDR monotherapy) on rectal and urethral complication probabilities, and suggest that it should be possible to improve the therapeutic ratio by exploiting joint LDR-EBRT planning. CONCLUSIONS: We describe new methodology for biologically based treatment planning for patients who receive combined low-dose-rate brachytherapy and external beam radiotherapy for prostate cancer. Using relevant mathematical tools, we demonstrate the feasibility of fusing dose distributions from each treatment for this combined regimen, which can then be expressed as isoeffective dose distributions. Based on this information, dose constraints for the rectum and urethra are described which could be used for planning such combination regimens.

Algorithms↗

Intensity-modulated radiotherapy as the boost or salvage treatment of nasopharyngeal carcinoma: the appropriate parameters in the inverse planning and the effect of patient's anatomic factors on the planning results.

The current study demonstrates that the large increase in normal tissue penalty often degrades target dose uniformity without a concomitant large improvement in normal tissue dose, especially in anatomically unfavorable patients. The excessively large normal tissue penalties do not improve treatment plans for patients having unfavorable geometry.

Carcinoma↗

Measurement of lung tumor motion using respiration-correlated CT.

PURPOSE: We investigate the characteristics of lung tumor motion measured with respiration-correlated computed tomography (RCCT) and examine the method's applicability to radiotherapy planning and treatment. METHODS AND MATERIALS: Six patients treated for non-small-cell lung carcinoma received a helical single-slice computed tomography (CT) scan with a slow couch movement (1 mm/s), while simultaneously respiration is recorded with an external position-sensitive monitor. Another 6 patients receive a 4-slice CT scan in a cine mode, in which sequential images are acquired for a complete respiratory cycle at each couch position while respiration is recorded. The images are retrospectively resorted into different respiration phases as measured with the external monitor (4-slice data) or patient surface displacement observed in the images (single-slice data). The gross tumor volume (GTV) in lung is delineated at one phase and serves as a visual guide for delineation at other phases. Interfractional GTV variation is estimated by scaling diaphragm position variations measured in gated radiographs at treatment with the ratio of GTV:diaphragm displacement observed in the RCCT data. RESULTS: Seven out of 12 patients show GTV displacement with respiration of more than 1 cm, primarily in the superior-inferior (SI) direction; 2 patients show anterior-posterior displacement of more than 1 cm. In all cases, extremes in GTV position in the SI direction are consistent with externally measured extremes in respiration. Three patients show evidence of hysteresis in GTV motion, in which the tumor trajectory is displaced 0.2 to 0.5 cm anteriorly during expiration relative to inspiration. Significant (>1 cm) expansion of the GTV in the SI direction with respiration is observed in 1 patient. Estimated intrafractional GTV motion for gated treatment at end expiration is 0.6 cm or less in all cases; however; interfraction variation estimates (systematic plus random) are more than 1 cm in 3/9 patients. CONCLUSION: Respiration-correlated CT can be performed with currently available CT equipment and acquisition settings. RCCT provides not only three-dimensional information on intrafractional tumor motion and deformation, but also allows estimates of interfractional tumor variation when combined with radiographic measurements of diaphragm position variation during treatment.

Carcinoma, Non-Small-Cell Lung↗

The CT motion quantitation of lung lesions and its impact on PET-measured SUVs.

UNLABELLED: We previously reported that respiratory motion is a major source of error in quantitation of lesion activity using combined PET/CT units. CT acquisition of the lesion occurs in seconds, rather than the 4-6 min required for PET emission scans. Therefore, an incongruent lesion position during CT acquisition will bias activity estimates using PET. In this study, we systematically analyzed the range of activity concentration changes, hence SUV, for lung lesions. METHODS: Five lung cancer patients were scanned with PET/CT. In CT, data were acquired in correlation with the real-time positioning. CT images were acquired, in cine mode, at 0.45-s intervals for slightly longer (1 s) than a full respiratory cycle at each couch position. Other scanning parameters were a 0.5-s gantry rotation, 140 kVp, 175 mA, 10-mm couch increments, and a 2.5-mm slice thickness. PET data were acquired after intravenous injection of about 444-555 MBq of (18)F-FDG with a 1-h uptake period. The scanning time was 3 min per bed position for PET. Regularity in breathing was assisted by audio coaching. A commercial software program was then used to sort the acquired CT images into 10 phases, with 0% corresponding to end of inspiration (EI) and 50% corresponding to end of expiration (EE). Using the respiration-correlated CT data, images were rebinned to match the PET slice locations and thickness. RESULTS: We analyzed 8 lesions from 5 patients. Reconstructed PET emission data showed up to a 24% variation in the lesion maximum standardized uptake values (SUVs) between EI and EE phases. Examination of all the phases showed an SUV variation of up to 30%. Also, in some cases the lesion showed up to a 9-mm shift in location and up to a 21% reduction in size when measured from PET during the EI phase, compared with during the EE phase. CONCLUSION: Using respiration-correlated CT for attenuation correction, we were able to quantitate the fluctuations in PET SUVs. Because those changes may lead to estimates of lower SUVs, the respiratory phase during CT transmission scanning needs to be measured or lung motion has to be regulated for imaging lung cancer in routine clinical practice.

Aged↗

Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy.

PURPOSE: To analyze acute lung toxicity data of non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy in terms of dosimetric variables, location of dose within subvolumes of the lungs, and models of normal-tissue complication probability (NTCP). METHODS AND MATERIALS: Dose distributions of 49 non-small-cell lung cancer patients treated in a dose escalation protocol between 1992 and 1999 were analyzed (dose range: 57.6-81 Gy). Nine patients had RTOG Grade 3 or higher acute lung toxicity. Correlation with dosimetric and physical variables, as well as Lyman and parallel NTCP models, was assessed. Lungs were evaluated as a single structure, as superior and inferior halves (to assess significance of dose to upper and lower lungs), and as ipsilateral and contralateral lungs. RESULTS: For the whole lung, Grade 3 or higher pneumonitis was significantly correlated (p 0.5 for superior lung indices, and >0.1 for contralateral lung indices studied). CONCLUSIONS: For these patients, commonly used dosimetric and NTCP models are significantly correlated with >or= Grade 3 pneumonitis. Equivalently strong correlations are found in the lower portion of the lungs and the ipsilateral lung, but not in the upper portion or contralateral lung.

Analysis of Variance↗

Evaluation of deep inspiration breath-hold lung treatment plans with Monte Carlo dose calculation.

PURPOSE: To evaluate dosimetry of deep inspiration breath-hold (DIBH) relative to free breathing (FB) for three-dimensional conformal radiation therapy of lung cancer with 6-MV photons and Monte Carlo (MC) dose calculations. METHODS AND MATERIALS: Static three-dimensional conformal radiation therapy, 6-MV plans, based on DIBH and FB CT images for five non-small-cell lung cancer patients, were generated on a clinical treatment planning system with equivalent path length tissue inhomogeneity correction. Margins of gross to planning target volume were not reduced for DIBH plans. Cord and lung toxicity determined the maximum treatment dose for each plan. Dose distributions were recalculated for the same beams with an MC dose calculation algorithm and electron density distributions derived from the CT images. RESULTS: MC calculations showed decreased target coverage relative to treatment-planning system predictions. Lateral disequilibrium caused more degradation of target coverage for DIBH than for FB (approximately 4% worse than expected for FB vs. 8% for DIBH). However, with DIBH higher treatment doses could be delivered without violating normal tissue constraints, resulting in higher total doses to gross target volume and to >99% of planning target volume. CONCLUSIONS: If DIBH enables prescription dose increases exceeding 10%, MC calculations indicate that, despite lateral disequilibrium, higher doses will be delivered to medium-to-large, partly mediastinal gross target volumes, providing that 6-MV photons are used and margins are not reduced.

Adult↗

Intensity-modulated radiotherapy versus conventional three-dimensional conformal radiotherapy for boost or salvage treatment of nasopharyngeal carcinoma.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new-onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally recurrent NPC. METHODS AND MATERIALS: Between January 14 and February 23, 2000, 5-field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The planning data of these patients were later transferred to Memorial Sloan-Kettering Cancer Center, where new IMRT plans, also using 5-7 radiation fields were created for each patient using an inverse treatment planning system. The IMRT and 3D-CRT plans were compared for all 14 patients. The relationship between the anatomic shapes and locations of targets and the results of different plans were studied. RESULTS: Target doses were more homogeneous in IMRT plans. The average maximal brainstem dose (D(05), the dose received by 5% of the brainstem volume) decreased from 30.9% of the prescription dose with 3D-CRT to 15.3% and 14.7% with 5- and 7-field IMRT, respectively (p = 0.004 and 0.003, respectively, compared with 3D-CRT, paired Student's t test). Five anatomic factors were found that predicted greater benefits with IMRT. These factors were (1) vertical length of target >7 cm, (2) minimal distance between target and brainstem <0.1 cm, (3) maximal AP overlap of target and brainstem >0.6 cm, (4) maximal AP overlap of target and spinal cord >1 cm, and (5) vertical overlap of target and eyes >0 cm. For the 7 patients with at least 1 of these 5 anatomic factors, the benefits achieved by IMRT planning would have been greater than the benefits for the other 7 patients (p = 0.005, Fisher's exact test). CONCLUSION: For boost or salvage treatment of NPC, lower normal tissue doses and more homogeneous target doses were achieved with IMRT plans. For NPC patients with at least 1 of the 5 anatomic factors, IMRT is highly recommended.

Algorithms↗

Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET).

PURPOSE: Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as part of their treatment. Three-dimensional conformal radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately delineate the target lesion and normal tissues. Clinical studies, however, indicate that positron emission tomography (PET) has higher sensitivity than CT in detecting and staging of mediastinal metastases. Imaging with fluoro-2-deoxyglucose (FDG) PET in conjunction with CT, therefore, can improve the accuracy of lesion definition. In this pilot study, we investigated the potential benefits of incorporating PET data into the conventional treatment planning of NSCLC. Case-by-case, we prospectively analyzed planning target volume (PTV) and lung toxicity changes for a cohort of patients. MATERIALS AND METHODS: We have included 11 patients in this study. They were immobilized in the treatment position and CT simulation was performed. Following CT simulation, PET scanning was performed in the treatment position using the same body cast that was produced for CT simulation and treatment. The PTV, along with the gross target volume (GTV) and normal organs, was first delineated using the CT data set. The CT and PET transmission images were then registered in the treatment planning system using either manual or automated methods, leading to consequent registration of the CT and emission images. The PTV was then modified using the registered PET emission images. The modified PTV is seen simultaneously on both CT and PET images, allowing the physician to define the PTV utilizing the information from both data sets. Dose-volume histograms (DVHs) for lesion and normal organs were generated using both CT-based and PET+CT-based treatment plans. RESULTS: For all patients, there was a change in PTV outline based on CT images versus CT/PET fused images. In seven out of 11 cases, we found an increase in PTV volume (average increase of 19%) to incorporate distant nodal disease. Among these patients, the highest normal-tissue complication probability (NTCP) for lung was 22% with combined PET/CT plan and 21% with CT-only plan. In other four patients PTV was decreased an average of 18%. The reduction of PTV in two of these patients was due to excluding atelectasis and trimming the target volume to avoid delivering higher radiation doses to nearby spinal cord or heart. CONCLUSIONS: The incorporation of PET data improves definition of the primary lesion by including positive lymph nodes into the PTV. Thus, the PET data reduces the likelihood of geographic misses and hopefully improves the chance of achieving local control.

Adult↗

Intensity-modulated radiotherapy.

Intensity-modulated radiotherapy represents a recent advancement in conformal radiotherapy. It employs specialized computer-driven technology to generate dose distributions that conform to tumor targets with extremely high precision. Treatment planning is based on inverse planning algorithms and iterative computer-driven optimization to generate treatment fields with varying intensities across the beam section. Combinations of intensity-modulated fields produce custom-tailored conformal dose distributions around the tumor, with steep dose gradients at the transition to adjacent normal tissues. Thus far, data have demonstrated improved precision of tumor targeting in carcinomas of the prostate, head and neck, thyroid, breast, and lung, as well as in gynecologic, brain, and paraspinal tumors and soft tissue sarcomas. In prostate cancer, intensity-modulated radiotherapy has resulted in reduced rectal toxicity and has permitted tumor dose escalation to previously unattainable levels. This experience indicates that intensity-modulated radiotherapy represents a significant advancement in the ability to deliver the high radiation doses that appear to be required to improve the local cure of several types of tumors. The integration of new methods of biologically based imaging into treatment planning is being explored to identify tumor foci with phenotypic expressions of radiation resistance, which would likely require high-dose treatments. Intensity-modulated radiotherapy provides an approach for differential dose painting to selectively increase the dose to specific tumor-bearing regions. The implementation of biologic evaluation of tumor sensitivity, in addition to methods that improve target delineation and dose delivery, represents a new dimension in intensity-modulated radiotherapy research.

Abdominal Neoplasms↗