Predicting radiation response.
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Biomedical subjects
Publications and source records attributed to M V Graham.
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PURPOSE: For treatment of lung cancer, dose heterogeneity corrections and subsequent prescription alteration remain controversial. Previous dosimetry studies based on slab geometry with a single beam geometry do not represent the clinical situation. A circumscribed tumor within lung poses a more complex problem. Energy choice also remains controversial. METHODS AND MATERIALS: An anthropomorphic phantom was modified by replacing lung cylinders (2.5 and 5.0 cm diameters by 5.0 cm length) with muscle-equivalent cylinders. The phantom was scanned on a CT simulator. Gross, clinical, and planning target volumes (GTV, CTV, PTV1 including tumor and regional nodes, PTV2 including tumor only) were designated slice-by-slice. Three-dimensional planning was performed with large fields (AP/PA/RPO) covering PTV1 and boost fields optimized for each PTV2, for 6 and 18 MV photons. Homogeneous, Ratio-Tissue-Air-Ratio (RTAR), and convolution-adapted RTAR (CARTAR) calculation algorithms were tested. Film was placed between phantom slices at the "tumor" levels. The phantom was irradiated with monitor units corresponding to homogeneous calculations, based on a homogeneous prescription. Measured and calculated doses were compared by isodoses and dose volume histograms. Ionization chambers and TLDs were also used for some test cases. RESULTS: The measured minimum dose covering PTV2 was within 5% of the homogeneous prescription dose of 70 Gy for 6 MV photons, while a lower dose (89% of prescription dose) was measured for 18 MV. The algorithms overpredicted the minimum dose to PTV2 by 6-18%. If the monitor units had been reduced according to simplistic heterogeneous calculations, the small PTV2 would have only been covered by 58 Gy for 18 MV irradiation. Based on this, a clinician may opt to actually increase the prescribed dose, thereby offsetting decreased monitor units. None of the algorithms predicted the diffuse penumbra associated with 18 MV photons in lung. CONCLUSION: Before adjusting dose prescriptions based on heterogeneity corrections, realistic phantom studies must be performed. The accuracy and effect of the corrections must then be assessed. The deficient coverage of PTV2 by the 18 MV beam compares unfavorably with the slight increase (5%) in hot spots associated with 6 MV. Our studies support strong caution before reducing dose prescriptions based on simple algorithms.
Fifty-two of 2,315 patients (2.4%) with non-small cell lung cancer (NSLC) treated with radiation therapy at the Mallinckrodt Institute of Radiology and St. Luke's Hospital between 1975 and 1988 presented with local recurrence after definitive surgery. No patient received radiation therapy after surgery as part of initial treatment and none had evidence of distant metastases at the time of local recurrence. The median time to first recurrence was 14 months. At recurrence, patients presented with disease in the bronchial stump (eight patients), ipsilateral lung parenchyma (10), chest wall (six), regional lymph nodes (five), or some combination thereof (23). Sixty-five percent of patients had histologic evidence of recurrence. Radiation therapy consisted of > 5,000 cGy in conventional fractionation to areas of gross disease in 35 of 52 patients. Of 15 patients receiving > 6,000 cGy, 13 had a favorable--complete (CR) or partial (PR) response--tumor response to radiation therapy. Among these patients, local control was achieved in 70% of patients with marginal recurrences (i.e., stump, parenchyma, or chest wall) and in 50% with nodal recurrences. The median survival after radiation therapy for all patients was 8.5 months. The best indicators for long-term survival were the interval from initial surgery to first recurrence and tumor response to radiation therapy.
Despite the fact that lead poisoning is one of the most common pediatric health problems in the United States today, little is known about the prevalence and correlates of this disease among nonurban preschool children living in the southern United States. The purpose of this study was to measure the prevalence of abnormal lead levels and to explore the relationships between lead levels and gender, weight, hemoglobin, and ethnicity. Using a chart review protocol, data were collected from 81 charts of children enrolled in a Head Start program in Florida. The prevalence rate of elevated lead levels was 18.5%, a rate higher than that found in most previous research. No relationship was found between lead levels and gender, weight, hemoglobin, and ethnicity. The results highlight the importance of local screening efforts. Controversies in screening are discussed in this article in some detail with the aim of assisting health care providers make decisions about whether universal screening for lead levels in children is appropriate and whether use of the Centers for Disease Control questionnaire has sufficient value. Further study is needed regarding prevalence rates in different geographic areas in the United States, and factors associated with elevated lead levels.
PURPOSE: To conduct a dose escalation clinical study with topotecan and concurrent standard dose thoracic irradiation to assess its feasibility and toxicity in the treatment of patients with locally advanced, inoperable nonsmall cell lung cancer (NSCLCA). METHODS AND MATERIALS: Between April 1993 and August 1994, 12 patients with inoperable, loco-regionally advanced NSCLCA were entered in a prospective dose escalation trial and assigned to receive concurrent thoracic radiotherapy and topotecan. Patients received thoracic irradiation to a total tumor dose of 60 Gy in 30 fractions. Initial fields were to encompass the gross disease plus the mediastinum. Topotecan was delivered by bolus injection days 1 through 5, and days 22 through 26, beginning on the same day as the radiation therapy. The initial dose level was 0.5 mg/m2. Two additional dose levels of 0.75 mg/m2 and 1.0 mg/m2 were tested. RESULTS: Six patients were accessioned to the 0.5 mg/m2 dose level, three patients to the 0.75 mg/m2 dose level, and three patients to the 1.0 mg/m2 dose level. At the 0.5 mg/m2 dose level, zero of six patients had > or = Grade 4 hematologic toxicity. One of the six had Grade 3 esophagitis. At the 0.75 mg/m2 dose level, two of three patients had > or = Grade 3 nonhematologic toxicity including anorexia, fatigue, nausea, vomiting, and weakness; zero patients experienced > or = Grade 4 hematologic toxicity. At the 1.0 mg/m2 dose level one of three patients had > or = Grade 3 esophagitis, and two of three patients experienced Grade 4 neutropenia. With a follow-up of 12 to 24 months, two patients are alive and free of disease, three patients are alive with disease (two with distant metastasis, one with local disease and distant metastasis), and the remaining seven patients are dead of disease. CONCLUSIONS: The combination of topotecan and thoracic radiotherapy for nonsmall lung cancer, in the manner given by this protocol, could be safely given at a dose level of only 0.5 mg/m2 days 1 to 5 and 22 to 26 with 60 Gy of external beam radiotherapy. Higher doses of topotecan were associated with high hematologic and gastrointestinal toxicity. Distant metastasis was the primary pattern of failure.
PURPOSE: To determine whether the clinical implementation of an electronic portal imaging device can improve the precision of daily external beam radiotherapy. METHODS AND MATERIALS: In 1991, an electronic portal imaging device was installed on a dual energy linear accelerator in our clinic. After training the radiotherapy technologists in the acquisition and evaluation of portal images, we performed a randomized study to determine whether online observation, interruption, and intervention would result in more precise daily setup. The patients were randomized to one of two groups: those whose treatments were actively monitored by the radiotherapy technologists and those that were imaged but not monitored. The treating technologists were instructed to correct the following treatment errors: (a) field placement error (FPE) > 1 cm; (b) incorrect block; (c) incorrect collimator setting; (d) absent customized block. Time of treatment delivery was recorded by our patient tracking and billing computers and compared to a matched set of patients not participating in the study. After the patients radiation therapy course was completed, an offline analysis of the patient setup error was planned. RESULTS: Thirty-two patients were treated to 34 anatomical sites in this study. In 893 treatment sessions, 1,873 fields were treated (1,089 fields monitored and 794 fields unmonitored). Ninety percent of the treated fields had at least one image stored for offline analysis. Eighty-seven percent of these images were analyzed offline. Of the 1,011 fields imaged in the monitored arm, only 14 (1.4%) had an intervention recorded by the technologist. Despite infrequent online intervention, offline analysis demonstrated that the incidence of FPE > 10 mm in the monitored and unmonitored groups was 56 out of 881 (6.1%) and 95 out of 595 (11.2%), respectively; p < 0.01. A significant reduction in the incidence of FPE > 10 mm was confined to the pelvic fields. The time to treat patients in this study was 10.78 min (monitored) and 10.10 min (unmonitored). Features that were identified that prevented the technologists from recognizing more errors online include poor image quality inherent to the portal imaging device used in this study, artifacts on the portal images related to table supports, and small field size lacking sufficient anatomical detail to detect FPEs. Furthermore, tools to objectively evaluate a portal image for the presence of field placement error were lacking. These include magnification factor corrections between the simulation of portal image, online measurement tools, image enhancement tools, and image registration algorithms. CONCLUSION: The use of an electronic portal imaging device in our clinic has been implemented without a significant increase in patient treatment time. Online intervention and correction of patient positioning occurred rarely, despite FPEs of > 10 mm being present in more than 10% of the treated fields. A significant reduction in FPEs exceeding 10 mm was made in the group of patients receiving pelvic radiotherapy. It is likely that this improvement was made secondarily to a decrease in systematic error and not because of online interventions. More significant improvements in portal image quality and the availability of online image registration tools are required before substantial improvements can be made in patient positioning with online portal imaging.
PURPOSE: Evaluation of three dimensional (3D) radiotherapy plans is difficult because it requires the review of vast amounts of data. Selecting the optimal plan from a set of competing plans involves making trade-offs among the doses delivered to the target volumes and normal tissues. The purpose of this study was to test an objective plan-evaluation model and evaluate its clinical usefulness in 3D treatment planning for nonsmall cell lung cancer. METHODS AND MATERIALS: Twenty patients with inoperable nonsmall cell lung cancer treated with definitive radiotherapy were studied using full 3D techniques for treatment design and implementation. For each patient, the evaluator (the treating radiation oncologist) initially ranked three plans using room-view dose-surface displays and dose-volume histograms, and identified the issues that needed to be improved. The three plans were then ranked by the objective plan-evaluation model. A figure of merit (FOM) was computed for each plan by combining the numerical score (utility in decision-theoretic terms) for each clinical issue. The utility was computed from a probability of occurrence of the issue and a physician-specific weight indicating its clinical relevance. The FOM was used to rank the competing plans for a patient, and the utility was used to identify issues that needed to be improved. These were compared with the initial evaluations of the physician and discrepancies were analyzed. The issues identified in the best treatment plan were then used to attempt further manual optimization of this plan. RESULTS: For the 20 patients (60 plans) in the study, the final plan ranking produced by the plan-evaluation model had an initial 73% agreement with the ranking provided by the evaluator. After discrepant cases were reviewed by the physician, the model was usually judged more objective or "correct." In most cases the model was also able to correctly identify the issues that needed improvement in each plan. Subsequent replanning confirmed that further manual plan optimization could be achieved in 17 patients. CONCLUSION: The objective plan-evaluation model was able to rank lung cancer radiotherapy plans from best to worst. It was useful in improving plans and may be useful to physicians in defining goals for patients based on the ability to effectively and safely treat their tumors.
PURPOSE: This is a prospective study to evaluate toxicity and efficacy of concurrent irradiation and three cycles of chemotherapy bolus cisplatin and infusion 5-fluorouracil (5FU) in patients with advanced gynecologic malignancies. MATERIALS AND METHODS: Patients received cisplatin, 50 mg/m2 I.V. rapid infusion, and 5-day continuous infusion of 5FU (750 mg/m2 per day (schedule A); or cisplatin 75 mg/m2 i.v. rapid infusion, and 4-day continuous infusion of 5FU 1,000 mg/m2 per day (schedule B). Schedule A was given to 25 patients in the first 36 months of the study and was changed to schedule B in an additional 42 patients. All patients received irradiation, which usually consisted of 20 Gy whole pelvis, 30-40 Gy split field, and two intracavitary insertions for a total of 80-90 Gy to point A. Primary cervical cancer occurred in 40 patients with 3 having stage IB bulky, 2 with stage IIA, 5 with stage IIB, 2 with stage IIIA, 23 with stage IIIB, 4 with stage IV, and 1 with stage IVB. Recurrent cervical carcinoma after radical hysterectomy occurred in 18 patients. The remainder of the patients consisted of two each with stages III and IV endometrial carcinoma, two with stage III vaginal carcinoma, two with stage III vulvar carcinoma, and one with recurrent vulvar carcinoma. Patients were treated from 1985 through 1992. RESULTS: The 5-year overall survivals for patients with stages IB (bulky)-IIB cervical cancer was 70%, 25% for stages IIIA-IVA, and 39% for patients with recurrent cervical carcinoma. All four patients with endometrial carcinoma have recurred and died. Two patients with vulvar carcinoma are alive and free of disease, and one is dead of intercurrent disease. One patient with stage III vaginal carcinoma is alive and free of disease, while the other recurred and died. No significant differences were observed in the toxicity of the two chemotherapy schedules. There were 9/39 (23%) grade 4 and one fatal complication in those with primary cervical carcinoma. The overall fistulae rate was 11% (4/39) with three patients developing rectovaginal fistulae and one having vesicovaginal fistula. CONCLUSION: Concurrent chemotherapy and irradiation for advanced gynecologic malignancies as administered in this study is highly toxic and fails to demonstrate an obvious survival improvement.
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Explore the source record for details and available documents.
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PURPOSE: To evaluate the preliminary results of a prospective trial using three-dimensional (3D) treatment for lung cancer. METHODS AND MATERIALS: Seventy patients with inoperable Stage I through IIIB lung cancer were treated with three-dimensional thoracic irradiation with or without chemotherapy (35% received chemotherapy). Total prescribed dose to the tumor ranged from 60-74 Gy (uncorrected for lung density). All patients were evaluated for local control, survival, and development of pneumonitis. These parameters were evaluated in respect to and compared with three-dimensional parameters used in their treatment planning. RESULTS: With a minimum follow-up of 6 to 30 months, the 2-year cause-specific survival rate for Stages I and II was 90% and 53% for Stage III (no difference between Stages IIIA and IIIB). Patients with local tumor control had a better 2-year overall survival rate (47%) than those with local failure (31%). Volumetrically heterogeneously calculated doses were important to the accurate delineation of dose-volume coverage as there was a wide range of discrepancies between a homogeneously prescribed point dose calculation and the heterogeneously calculated volume coverage of that prescription. High-grade pneumonitis was correlated with the location of the tumor with lower lobe tumors having a much higher risk than those with upper lobe tumors. A critical volume effect and threshold dose were apparent in the development of high-grade pneumonitis. CONCLUSIONS: Three-dimensional therapy for lung cancer has been practically implemented at the Mallinckrodt Institute of Radiology and shows promising results in our preliminary analysis. The incidence of high-grade pneumonitis, however, warrants careful selection of patients for future dose escalation. Future dose escalation trials in lung cancer should be directed to volumes that limit the amount of elective nodal irradiation. However, the volume of necessary elective nodal irradiation remains unknown and should be studied prospectively. Dose escalation trials are indicated and may be facilitated by smaller target volumes.
PURPOSE: This pilot study was undertaken to evaluate the effect of high dose-per-fraction radiotherapy given to the tumor primary concurrently with conventional fractionated radiotherapy to the electively irradiated regional lymph nodes (concomitant boost). This article reports the late results of toxicity and survival. METHODS AND MATERIALS: Fifty-nine patients with histologically proven clinical Stage T3-T4, N1-3 nonsmall cell lung cancer were prospectively enrolled in this study. Fifty-six were evaluable for late effects. The treatment delivered 2.68 Gy daily to the primary tumor, 5 days a week, to a total dose of 75 Gy in 28 fractions in 5.5 weeks. At the same treatment sessions, the electively irradiated nodal areas received 1.8 Gy daily, 5 days per week, to a total dose of 50.4 Gy. All doses were calculated with heterogeneity corrections for lung density. RESULTS: Presently, one patient remains alive at 7.7 years. Median survival was 10.0 months with 1-, 2-, 3-, and 5-year survival rates of 41%, 25%, 18%, and 4%, respectively. Three patients developed severe late complications, including pulmonary fibrosis and osteonecrosis. The remainder of the patients, however, developed only grade 1 or 2 pulmonary fibrosis and/or pneumonitis. CONCLUSION: We conclude that concomitant boost radiotherapy in the manner reported resulted in acceptable late toxicity. The 2- and 3-year survivals compared favorably with the best-reported results in the literature with either hyperfractionated or chemoradiotherapy treatment. Studies that deliver higher radiotherapy doses to the gross tumor combined with chemotherapy are in order.
PURPOSE: We have developed a software tool for interactively verifying treatment plan implementation. The Electronic View Box (EVB) tool copies the paradigm of current practice but does so electronically. A portal image (online portal image or digitized port film) is displayed side by side with a prescription image (digitized simulator film or digitally reconstructed radiograph). The user can measure distances between features in prescription and portal images and "write" on the display, either to approve the image or to indicate required corrective actions. The EVB tool also provides several features not available in conventional verification practice using a light box. METHODS AND MATERIALS: The EVB tool has been written in ANSI C using the X window system. The tool makes use of the Virtual Machine Platform and Foundation Library specifications of the NCI-sponsored Radiation Therapy Planning Tools Collaborative Working Group for portability into an arbitrary treatment planning system that conforms to these specifications. The present EVB tool is based on an earlier Verification Image Review tool, but with a substantial redesign of the user interface. A graphical user interface prototyping system was used in iteratively refining the tool layout to allow rapid modifications of the interface in response to user comments. RESULTS: Features of the EVB tool include 1) hierarchical selection of digital portal images based on physician name, patient name, and field identifier; 2) side-by-side presentation of prescription and portal images at equal magnification and orientation, and with independent grayscale controls; 3) "trace" facility for outlining anatomical structures; 4) "ruler" facility for measuring distances; 5) zoomed display of corresponding regions in both images; 6) image contrast enhancement; and 7) communication of portal image evaluation results (approval, block modification, repeat image acquisition, etc.). CONCLUSION: The EVB tool facilitates the rapid comparison of prescription and portal images and permits electronic communication of corrections in port shape and positioning.
Preliminary clinical results are presented for 209 patients with cancer who had treatment planned on our three-dimensional radiation treatment planning (3-D RTP) system and were treated with external beam conformal radiation therapy. Average times (min) for CT volumetric simulation were: 74 without or 84 with contrast material; 36 for contouring of tumor/target volume and 44 for normal anatomy; 78 for treatment planning; 53 for plan evaluation/optimization; and 58 for verification simulation. Average time of daily treatment sessions with 3-D conformal therapy or standard techniques was comparable for brain, head and neck, thoracic, and hepatobiliary tumors (11.8-14 min and 11.5-12.1, respectively). For prostate cancer patients treated with 3-D conformal technique and Cerrobend blocks, mean treatment time was 19 min; with multileaf collimation it was 14 min and with bilateral arc rotation, 9.8 min. Acute toxicity was comparable to or lower than with standard techniques. Sophisticated 3-D RTP and conformal irradiation can be performed in a significant number of patients at a reasonable cost. Further efforts, including dose-escalation studies, are necessary to develop more versatile and efficient 3-D RTP systems and to enhance the cost benefit of this technology in treatment of patients with cancer.
An easy-to-use decision support tool for staffing is explained. By combining information from a hospital's patient classification system with the hospital's usual staffing policies, a graph can be developed that shows immediately whether a unit is economically justified in using overtime or contract nurses, or if nurses are available from other units.
PURPOSE: The objective of this study is to use daily electronic portal imaging to evaluate weekly port filming in detecting patient set-up position. METHODS AND MATERIALS: A computer-based portal alignment method was used to quantify the field displacements on 191 digitized weekly port films and 848 daily electronic portal images in 21 radiation therapy patients. An electronic portal image data set as a control for actual daily treatment position was used to evaluate weekly port films with respect to same-day field displacement, rate of field placement error detection, and prediction of subsequent daily field displacements. RESULTS: The field displacements measured on a port film frequently deviated from the corresponding field displacements on the electronic portal image obtained in the same treatment set-up. A linear regression analysis showed that the curves fitted to the same-day field displacements had slopes that differed significantly from unity (p < 0.001). Overall, the respective frequencies of field placement error, beyond clinical tolerance limits of 5, 7, and 10 mm (corresponding to head and neck, thoracic, and pelvic sites) for port filming and electronic portal imaging were 11% and 14% (p = 0.4) in the X-direction (lateral or anteroposterior) and 24% and 13% (p = .0001) in the Y-direction (caphalad-caudad). When the data were broken down by anatomical region, this discrepancy was found to be mainly due to the differences in the thorax, and head and neck image data sets. For thoracic fields, error in Y-shifts was 28% by port filming, but only 9% by portal imaging (p = 0.01). In the head and neck region, 18% of the port films exceeded tolerance, whereas only 6% of the electronic portal images did (p = 0.0001). Field displacements on the treatment set-ups between the acquisition of port films were not predicted by those films. CONCLUSION: There are discrepancies between the field displacements and field placement errors detected by weekly port films and daily electronic portal images. This study suggests that improved methods of treatment verification may be necessary in modern radiation therapy.
PURPOSE: Several reports in the literature suggest that local-regional control and possibly survival could be improved for inoperable nonsmall cell lung cancer if the radiation dose to the target volume could be increased. Higher doses, however, bring with them the potential for increased side effects and complications of normal tissues. Three-dimensional treatment planning has shown significant potential for improving radiation treatment planning in several sites, both for tumor coverage and for sparing of normal tissue from high doses of radiation and, thus, has the potential of developing radiation therapy techniques that result in uncomplicated local-regional control of lung cancer. We have studied the feasibility of large-scale implementation of true three-dimensional technologies in the treatment of patients with cancers of the thorax. METHODS AND MATERIALS: CT scans were performed on 10 patients with inoperable nonsmall cell lung cancer to obtain full volumetric image data, and therapy was planned on our three-dimensional radiotherapy treatment planning system. Target volumes were determined using the new ICRU nomenclature--Gross Tumor Volume, Clinical Target Volume, and Planning Target Volume. Plans were performed according to our standard treatment policies based on traditional two-dimensional radiotherapy treatment planning methodologies and replanned using noncoplanar three-dimensional beam techniques. The results were quantitatively compared using dose-volume histograms, dose-surface displays, and dose statistics. RESULTS: Target volume delineation remains a difficult problem for lung cancer. Defining Gross Tumor Volume and Clinical Target Volume may depend on window and level settings of the three-dimensional radiotherapy treatment planning system, suggesting that target volume delineation on hard copy film is inadequate. Our study shows that better tumor coverage is possible with three-dimensional plans. Dose to critical structures (e.g., the heart) could often be reduced (or at least remain acceptable) using noncoplanar beams even with dose escalation to 75 to 80 Gy for the planning volume surrounding the Gross Target Volume. CONCLUSION: Commonly used beam arrangements for treatment of lung cancer appear to be inadequate to safely deliver tumor doses of higher than 70 Gy. Although conventional treatment techniques may be adequate for tumor coverage, they are inadequate for sparing of normal tissues when the prescription dose is escalated. The ability to use noncoplanar fields for such patients is a major advantage of three-dimensional planning. This capability led to better tumor coverage and reduced dose to critical normal tissues. However, this advantage was achieved at the expense of a greater time commitment by the treatment planning staff (particularly the radiation oncologist) and a greater complexity of treatment delivery. In summary, three-dimensional radiotherapy treatment planning appears to provide the radiation oncologist with the necessary tools to increase tumor dose, which may lead to increased local-regional control in patients with lung cancer while maintaining normal tissue doses at acceptable tolerance levels.