Automatic selection of non-coplanar beam directions for three-dimensional conformal radiotherapy.

An algorithm is described, based on ray-tracing and the beam's-eye-view, that exhaustively searches all permitted beam directions. The evaluation of the search is based on a general cost function that can be adapted to the clinical objectives by means of parameters and weighting factors. The approach takes into account the constraints of the linear accelerator by discarding beam directions that are not permitted. A sensitivity analysis was carried out to determine appropriate parameters for different sized organs, and a prostate case was used to benchmark the approach. The algorithm was also applied to two clinical cases (brain and sinus) to test the benefits of the approach compared with manual angle selection. The time to perform a beam direction search was approximately 2 min for the coplanar and 12 min for the non-coplanar beam space. The angles obtained for the prostate case compared well with reports in the literature. For the brain case, the mean dose to the right and left optic nerves was reduced by 12% and 50%, respectively, whilst the target dose uniformity was improved. For the sinus case, the mean doses to the right and left parotid glands were reduced by 54% and 46%, respectively, to the right and left optic nerves by 37% and 62%, respectively, and to the optic chiasm by 39%, whilst the target dose uniformity was also improved. For the clinical cases the plans based on optimized beam directions were simpler and resulted in better sparing of critical structures compared with plans based on manual angle selection. The approach provides a practical alternative to elaborate and time consuming beam angle optimization schemes and is suitable for routine clinical usage.

18fluorodeoxyglucose positron emission tomography to detect mediastinal or internal mammary metastases in breast cancer.

PURPOSE: To determine the prevalence of suspected disease in the mediastinum and internal mammary (IM) node chain by 18fluorodeoxyglucose (FDG) positron emission tomography (PET), compared with conventional staging by computed tomography (CT) in patients with recurrent or metastatic breast cancer. PATIENTS AND METHODS: We retrospectively evaluated intrathoracic lymph nodes using FDG PET and CT data in 73 consecutive patients with recurrent or metastatic breast cancer who had both CT and FDG PET within 30 days of each other. In reviews of CT scans, mediastinal nodes measuring 1 cm or greater in the short axis were considered positive. PET was considered positive when there were one or more mediastinal foci of FDG uptake greater than the mediastinal blood pool. RESULTS: Overall, 40% of patients had abnormal mediastinal or IM FDG uptake consistent with metastases, compared with 23% of patients who had suspiciously enlarged mediastinal or IM nodes by CT. Both FDG PET and CT were positive in 22%. In the subset of 33 patients with assessable follow-up by CT or biopsy, the sensitivity, specificity, and accuracy for nodal disease was 85%, 90%, and 88%, respectively, by FDG PET; 54%, 85%, and 73%, respectively, by prospective interpretation of CT; and 50%, 83%, and 70%, respectively, by blinded observer interpretation of CT. Among patients suspected of having only locoregional disease recurrence (n = 33), 10 had unsuspected mediastinal or IM disease by FDG PET. CONCLUSION: FDG PET may uncover disease in these nodal regions not recognized by conventional staging methods. Future prospective studies using histopathology for confirmation are needed to validate the preliminary findings of this retrospective study.

Concurrent radiation therapy and paclitaxel or docetaxel chemotherapy in high-risk breast cancer.

PURPOSE: Evidence supports the inclusion of the taxanes in the treatment of breast cancer. A recent randomized trial has shown a survival advantage to the addition of paclitaxel in the adjuvant treatment of node-positive patients. Several studies have suggested diminished local control if adjuvant radiation is delayed, while in vitro and in vivo studies have demonstrated a benefit of concurrent administration of taxanes with radiation. For these reasons, we began in 1995 to administer radiation therapy concurrently with the taxanes in advanced breast cancer. This retrospective review examines the feasibility of such treatment. METHODS AND MATERIALS: Forty-four patients were treated with concurrent radiation and either paclitaxel (29 patients) or docetaxel (15 patients). One patient received both paclitaxel and docetaxel. Eighteen patients were treated for recurrent disease, 9 had received prior radiation. Toxicity was assessed by the RTOG scale for acute and late effects. RESULTS: Concurrent radiation and taxane chemotherapy was well tolerated. Nine patients (20%) experienced Grade 3 acute skin toxicity. This was more likely with docetaxel than paclitaxel (p = 0. 04). Among patients undergoing breast conservation, there were no Grade 3 toxicities. With a median follow-up of 11 months, 1 patient has developed breast fibrosis. CONCLUSION: Concurrent administration of both paclitaxel and docetaxel with radiation resulted in acceptable toxicity. Overall, the acute skin toxicity seen with docetaxel was more pronounced. However, among patients undergoing breast conservation the taxanes were both well tolerated. Further study is necessary to assess the impact of concurrent treatment on long-term outcome.

Anatomical information in radiation treatment planning.

We report on experience and insights gained from prototyping, for clinical radiation oncologists, a new access tool for the University of Washington Digital Anatomist information resources. This access tool is designed to integrate with a radiation therapy planning (RTP) system in use in a clinical setting. We hypothesize that the needs of practitioners in a clinical setting are different from the needs of students, the original targeted users of the Digital Anatomist system, but that a common knowledge resource can serve both. Our prototype was designed to help define those differences and study the feasibility of a full anatomic reference system that will support both clinical radiation therapy and all the existing educational applications.

Non-physician practitioners in radiation oncology: advanced practice nurses and physician assistants.

PURPOSE: With changes in reimbursement and a decrease in the number of residents, there is a need to explore new ways of achieving high quality patient care in radiation oncology. One mechanism is the implementation of non-physician practitioner roles, such as the advanced practice nurse (APN) and physician assistant (PA). This paper provides information for radiation oncologists and nurses making decisions about: (1) whether or not APNs or PAs are appropriate for their practice, (2) which type of provider would be most effective, and (3) how best to implement this role. METHODS: Review of the literature and personal perspective. CONCLUSIONS: Specific issues addressed regarding APN and PA roles in radiation oncology include: definition of roles, regulation, prescriptive authority, reimbursement, considerations in implementation of the role, educational needs, and impact on resident training. A point of emphasis is that the non-physician practitioner is not a replacement or substitute for either a resident or a radiation oncologist. Instead, this role is a complementary one. The non-physician practitioner can assist in the diagnostic work-up of patients, manage symptoms, provide education to patients and families, and assist them in coping. This support facilitates the physician's ability to focus on the technical aspects of prescribing radiotherapy.

Value of combined FDG PET and MR imaging in the evaluation of suspected recurrent local-regional breast cancer: preliminary experience.

PURPOSE: To assess the performance and potential clinical effects of combined 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging of the axilla and brachial plexus in patients suspected of having local-regional breast cancer metastases. MATERIALS AND METHODS: Upper-body FDG PET and axillary and supraclavicular MR imaging were performed in 10 patients (age range, 45-71 years) with clinical findings suggestive of breast cancer metastases. Medical records were reviewed retrospectively. Imaging findings were correlated with clinical data and follow-up findings in all patients. Surgical findings were available in four patients. RESULTS: Nine patients had local-regional breast cancer metastases. MR imaging was diagnostic for tumor in five patients and was indeterminate in four patients with axillary or chest wall metastases. With FDG PET, metastatic tumor was positively identified in all nine patients. MR imaging was useful for determining the relationship of metastatic tumor to axillary and supraclavicular neurovascular structures. FDG PET helped confirm metastases in patients with indeterminate MR imaging findings and depicted unsuspected metastases outside the axilla. CONCLUSION: MR imaging and FDG PET are complementary in detecting and characterizing local-regional breast cancer metastases. Combined FDG PET and MR imaging provide useful treatment-planning data for patients clinically suspected of having recurrent axillary or supraclavicular breast cancer.

The use of medical images in planning and delivery of radiation therapy.

The authors provide a survey of how images are used in radiation therapy to improve the precision of radiation therapy plans, and delivery of radiation treatment. In contrast to diagnostic radiology, where the focus is on interpretation of the images to decide if disease is present, radiation therapy quantifies the extent of the region to be treated, and relates it to the proposed treatment using a quantitative modeling system called a radiation treatment planning (RTP) system. This necessitates several requirements of image display and manipulation in radiation therapy that are not usually important in diagnosis. The images must have uniform spatial fidelity: i.e., the pixel size must be known and consistent throughout individual images, and between spatially related sets. The exact spatial relation of images in a set must be known. Radiation oncologists draw on images to define target volumes; dosimetrists use RTP systems to superimpose quantitative models of radiation beams and radiation dose distributions on the images and on the sets of organ and target contours derived from them. While this mainly uses transverse cross-sectional images, projected images are also important, both those produced by the radiation treatment simulator and the treatment machines, and so-called "digital reconstructed radiographs," computed from spatially related sets of cross-sectional images. These requirements are not typically met by software produced for radiologists but are addressed by RTP systems. This review briefly summarizes ongoing work on software development in this area at the University of Washington Department of Radiation Oncology.

Prism: a new approach to radiotherapy planning software.

PURPOSE: We describe the capabilities and performance of Prism, an innovative new radiotherapy planning system with unusual features and design. The design and implementation strategies are intended to assure high quality and clinical acceptability. The features include Artificial Intelligence tools and special support for multileaf collimator (MLC) systems. The design provides unusual flexibility of operation and ease of expansion. METHODS AND MATERIALS: We have implemented Prism, a three-dimensional (3D) radiotherapy treatment-planning system on standard commercial workstations with the widely available X window system. The design and implementation use ideas taken from recent software engineering research, for example, the use of behavioral entity-relationship modeling and the "Mediator Method" instead of ad-hoc programming. The Prism system includes the usual features of a 3D planning system, including Beam's Eye View and the ability to simulate any treatment geometry possible with any standard radiotherapy accelerator. It includes a rule-based expert system for automated generation of the planning target volume as defined in ICRU Report 50. In addition, it provides special support for planning treatments with a multileaf collimator (MLC). We also implemented a Radiotherapy Treatment Planning Tools Foundation for Prism, so that we are able to use software tools form other institutions without any source code modification. RESULTS: The Prism system has been in clinical operation at the University of Washington since July 1994 and has been installed at several other clinics. The system is run simultaneously by several users, each with their own workstation operating from a common networked database and software. In addition to the dosimetrists, the system is used by radiation oncologists to define tumor and target volumes and by radiation therapists to select treatment setups to load into a computer controlled accelerator. CONCLUSIONS: Experience with the installation and operation has shown the design to be effective as both a clinical and research tool. Integration of software tools has eased the development and significantly enhanced the clinical usability of the system. The design has been shown to be a sound basis for further innovation in radiation treatment planning software and for research in the treatment planning process.

Evaluation of an expert system producing geometric solids as output.

This paper reports the evaluation of an expert system whose output is a three-dimensional geometric solid. Evaluating such an output emphasizes the problems of establishing a comparison standard, and of identifying and classifying deviations from that standard. Our evaluation design used a panel of physicians for the first task and a separate panel of expert judges for the second. We found that multi-parameter or multi-dimensional expert system outputs, such as this one, may result in lower overall performance scores and increased variation in acceptability to different physicians. We surmise that these effects are a consequence of the higher number of factors which may be deemed unacceptable. The effects appear, however, to be equal for computer and human output. This evaluation design is thus applicable to other expert systems producing similarly complex output.

Effect of delay in radiation in the combined modality treatment of breast cancer.

PURPOSE: To study how the timing of radiation influences local control, overall survival, and disease-free survival in patients being treated with chemotherapy and radiation for a local-regional carcinoma of the breast. METHODS AND MATERIALS: Over a ten year period, 105 patients received chemotherapy and radiation treatments for a local-regional breast cancer. The population was divided into two groups based on the timing of their radiation treatments. Forty-eight patients began their radiation within 6 months of their diagnosis (early radiation group). Fifty-seven patients had a delay in their radiation for 6 or greater months in order to first maximize chemotherapy treatments (delayed radiation group). There were no significant differences between the two groups with respect to nodal status, stage of the primary, estrogen receptor status, patient age, or type of surgery performed. The only prognostic parameter that was imbalanced was that of a greater percentage of patients with close or positive margins in the early radiation group compared to the delayed radiation group (69% versus 38%, p < 0.02). RESULTS: Comparisons of local control, overall survival, and disease-free survival between the early radiation patients and delayed radiation patients all favored the early radiation group. Respective 8-year actuarial rates were: local control--98% vs. 76%, p = 0.004; overall survival--80% vs. 52%, p = 0.016; disease-free survival--71% vs. 48%, p = 0.008. The differences continued to be significant in a multivariate Cox regression model comparison: p = 0.011, p = 0.050, p = 0.009. There was only one death from intercurrent disease, so that overall survival approximated cause-specific survival to an accurate degree. CONCLUSIONS: In patients requiring chemotherapy and radiation treatments for a local-regional breast cancer, a delay in the initiation of radiation for a period of 6 months or greater from diagnosis resulted in a higher local failure rate. Furthermore, this higher local failure rate was associated with an increased rate of distant metastases and a decreased overall survival rate.

Current use of electron beam therapy in the United States.

Owing to their physical characteristics, electron beams are a crucial component in radiotherapy of human tumors. Besides their main indications (skin cancers, head and neck tumors, breast, chest wall recurrence, low pelvic tumors) other types and sites of malignancies are to be considered: skin lymphomas, soft tissue sarcomas, Kaposi's sarcoma in AIDS patients, as well as Intra Operative Radiotherapy.

Transient and chronic neurological complications of fast neutron radiation for adenocarcinoma of the prostate.

The records of 132 patients participating in clinical trials using fast neutron (n = 94), mixed neutron and photon (n = 16), or conventional photon (n = 22) irradiation for primary management of prostatic cancer were retrospectively reviewed to assess treatment-related neurological complications. With a median follow-up of 14 months (range 1 to 101 months), 31/132 patients (26 neutron, 3 mixed beam, 2 photon) have experienced either sciatica beginning during or shortly after treatment, or diminished bladder or bowel continence that developed at a median time of 6.5 months following treatment. Sciatica responded to oral steroids and was usually self-limited, whereas sphincter dysfunction appears to be permanent. Pre-treatment risk factors for complications included a history of hypertension, diabetes, cigarette smoking or peripheral vascular disease, with 81% of affected patients having one or more risk factors compared with 55% of unaffected patients (p = 0.01). Seven patients have moderate (5) or severe (2) residual problems, all in the cohorts receiving neutrons (6/7) or mixed beam therapy (1/7).

Dose volume histogram analysis of liver radiation tolerance.

Eleven patients with carcinoma of the pancreas or biliary system received heavy charged particle radiation treatments and whole liver heavy charged particle radiation at Lawrence Berkeley Laboratory. Doses to the whole liver ranged from 10 to 24 Gray-equivalent (the biological equivalent of 10 to 24 Gray of low-LET photon radiation), whereas the dose to the primary lesion ranged from 53.5 to 70 Gray-equivalent (GyE). The fraction size was 2 to 3 GyE. The liver received partial as well as whole organ irradiation. Integral dose volume histograms for the liver were obtained in all 11 patients. An integral dose volume histogram displays on the ordinate the percentage of liver that was irradiated in excess of the dose specified on the abcissa. In this study, the clinical liver radiation tolerance of these patients is correlated with the information contained in an integral dose volume histogram. One patient developed radiation hepatitis. The integral dose volume histogram of this patient differed from the dose volume histograms of the other 10 patients. This difference was greatest in the range of doses between 30 and 40 GyE. Our results suggest that liver doses in excess of 30 to 35 GyE should be limited to 30% of the liver or less when 18 GyE of whole liver radiation is delivered at 2 GyE per fraction in addition to primary radiation of the pancreas or biliary system.

A phase I-II trial of heavy charged particle irradiation of malignant glioma of the brain: a Northern California Oncology Group Study.

Thirty-nine patients with primary or recurrent glioma of the brain were irradiated wholely or in part with heavy charged particle beams at the University of California Lawrence Berkeley Laboratory in a Phase I-II clinical trial of the Northern California Oncology Group. During the course of this trial, treatment techniques have been developed and tumor doses have been escalated in order to obtain data on normal brain toxicity and response of malignant glioma of the brain. Toxicity has been acceptable with a low level of brain injury. Survival and tumor control has been approximately the same as historical results in glioma of the brain. Further dose escalation is planned together with possible trial of combined modality therapy.

Radiotherapy of lymphoid diseases of the orbit.

Thirty-two patients with orbital pseudotumor (18), reactive lymphoid hyperplasia (2), atypical lymphoid infiltrate (4) or malignant lymphoma (8) were treated in the Division of Radiation Therapy at Stanford University between January 1973 and May 1983. Of the 20 patients with pseudotumor or reactive lymphoid hyperplasia, 10 had unilateral lesions and 10 had bilateral lesions. Biopsy samples were obtained in 15 patients; in five patients with bilateral disease the diagnosis was made on the basis of computed tomography (CT) and clinical findings. The majority of patients were referred because of disease refractory to treatment with corticosteroids. The patients were given a mean dose of 2360 rad using complex, individualized megavoltage techniques including lens shielding. Radiotherapy was well tolerated with no significant acute or late complications. Fifteen patients had complete resolution of symptoms after treatment; five had continued symptoms. Of the 12 patients with malignant lymphoma or atypical lymphoid infiltrate, four had systemic lymphoma with orbital involvement and eight had orbital involvement only. The diagnosis was made by biopsy in all patients and immunophenotyping was done in six cases, of which 5 were monoclonal. Patients were evaluated with a chest radiograph, lymphogram or abdominal CT, bone marrow biopsy and orbital CT. A mean dose of 3625 rad was delivered to the orbit only. Most of the patients received complex megavoltage treatment using bolus. All patients in this group had a complete response and local control. There were no relapses in those with localized disease. Two patients developed cataracts. Carefully planned orbital radiotherapy provides local control without symptomatic sequelae for orbital masses ranging from pseudotumor to malignant lymphoma.

Hodgkin's disease in patients over sixty years old.

Fifty-two patients 60 to 75 years of age were treated for Hodgkin's disease at Stanford University between 1968 and 1980. Adequate staging was defined as including a lymphogram and staging laparotomy for stage I to III and a positive bone marrow or liver biopsy or other evidence of diffuse involvement of extralymphatic tissues for stage IV. Adequate treatment was defined as subtotal lymphoid irradiation for pathologic stages I to IIA; total lymphoid irradiation for stages IIB to IIIA; and chemotherapy with or without irradiation for stages IIIB to IV. Twenty-four patients (46%) had advanced disease (IIIB to IV). Those patients who received appropriate treatment had a median survival of only 39 months. Of the 28 patients with limited disease (I to IIIA), 15 had laparotomy and adequate treatment. Thirteen did not have a laparotomy and 7 were treated with involved-field irradiation. The 5-year survival rate in the laparotomy-staged and adequately treated group was 86%, but in the clinically staged group, only 35% (p = 0.006).