Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.

Development and clinical implementation of an enhanced display algorithm for use in networked electronic portal imaging.

PURPOSE: To introduce and clinically validate a preprocessing algorithm that allows clinical images from an electronic portal imaging device (EPID) to be displayed on any computer monitor, without loss of clinical usability. The introduction of such a system frees EPI systems from the constraints of fixed viewing workstations and increases mobility of the images in a department. METHODS AND MATERIALS: The preprocessing algorithm, together with its variable parameters is introduced. Clinically, the algorithm is tested using an observer study of 316 EPID images of the pelvic region in the framework of treatment of carcinoma of the cervix and endometrium. Both anterior-posterior (AP/PA) and latero-lateral (LAT) images were used. The images scored were taken from six different patients, five of whom were obese, female, and postmenopausal. The result is tentatively compared with results from other groups. The scoring system, based on the number of visible landmarks in the port, is proposed and validated. Validation was performed by having the observer panel score images with artificially induced noise levels. A comparative study was undertaken with a standard automatic window and leveling display technique. Finally, some case studies using different image sites and EPI detectors are presented. RESULTS: The image quality for all images in this study was deemed to be clinically useful (mean score >1). Most of the images received a score which was second highest (AP/PA landmarks > or =6 and LAT landmarks > or =5). Obesity, which has been an important factor determining the image quality, was not seen to be a factor here. Compared to standard techniques a highly significant improvement was determined with regard to clinical usefulness. The algorithm performs fast (less than 9 seconds) and needs no additional user interaction in most of the cases. The algorithm works well on both direct detection portal imagers and camera-based imagers whether analog or digital cameras. CONCLUSIONS: We have demonstrated that it is possible to preprocess EPIs in such a way that the clinically relevant landmarks are easily detected on a generic computer screen. The algorithm is system-independent and fast. This allows for the encoding of EPIs in more generalized commercial formats so that distribution of images is facilitated.

Genitourinary anomalies in the CHARGE association.

PURPOSE: We identified the incidence and types of genital and urinary anomalies, and established a plan for evaluating the urinary system in the CHARGE association. MATERIALS AND METHODS: We retrospectively reviewed the charts of 32 patients in whom the CHARGE association was diagnosed. RESULTS: Of the 32 patients identified 22 (69%) had genitourinary abnormalities. Genital anomalies, including micropenis, penile agenesis, hypospadias, chordee, cryptorchidism, a bifid scrotum, atresia of the uterus, cervix and vagina, and hypoplastic labia majora, labia minora and clitoris, were present in 18 patients (56%). Of the 24 patients who underwent renal ultrasound 10 (42%) were diagnosed with urinary tract anomalies including a solitary kidney, hydronephrosis, renal hypoplasia and duplex kidneys. Further evaluation revealed vesicoureteral reflux, neurogenic bladder secondary to spinal dysraphism, nephrolithiasis, ureteropelvic junction obstruction and a nonfunctioning upper pole in both duplex kidneys. CONCLUSIONS: There is a high incidence of genitourinary anomalies in the CHARGE association. Because of this high incidence of anomalies, patients with this condition should undergo a careful genitourinary evaluation, including renal and bladder ultrasound, and voiding cystourethrography screening.

Outcome Assessment in Radiation Oncology.

Improvements in medical practice most often are based on the analysis of our past performance. With the increased emphasis in the United States on managed care, the examination of our clinical performance has taken on increased importance. In addition to traditional tumor registries and clinical trials, we are being asked to substantiate the quality of our practice for purchasers such as third-party intermediaries and industry. Data collection can often be done on existing departmental and hospital information resources. Industry-wide standards such as HL7 and DICOM further support this effort. Selection of the best computer hardware, networks, and software is critical to effective clinic and patient management.

Clinical results of computerized tomography-based simulation with laser patient marking.

PURPOSE: Accuracy of a patient treatment portal marking device and computerized tomography (CT) simulation have been clinically tested. METHODS AND MATERIALS: A CT-based simulator has been assembled based on a commercial CT scanner. This includes visualization software and a computer-controlled laser drawing device. This laser drawing device is used to transfer the setup, central axis, and/or radiation portals from the CT simulator to the patient for appropriate patient skin marking. A protocol for clinical testing is reported. Twenty-five prospectively, sequentially accessioned patients have been analyzed. RESULTS: The simulation process can be completed in an average time of 62 min. Under many cases, the treatment portals can be designed and the patient marked in one session. Mechanical accuracy of the system was found to be within +/- 1mm. The portal projection accuracy in clinical cases is observed to be better than +/- 1.2 mm. Operating costs are equivalent to the conventional simulation process it replaces. CONCLUSION: Computed tomography simulation is a clinical accurate substitute for conventional simulation when used with an appropriate patient marking system and digitally reconstructed radiographs. Personnel time spent in CT simulation is equivalent to time in conventional simulation.

CT-based simulation with laser patient marking.

A CT-based simulator has been assembled based on a commercial CT scanner, virtual simulation software developed at the University of North Carolina and a laser drawing device to transfer the radiation portals from the virtual simulator to the patient. The simulation process can be completed in approximately 1 h; under most cases, the treatment portals can be designed and the patient marked in one session. The device has an inherent accuracy of +/- 1 mm. The portal projection accuracy in clinical cases is observed to be better than 2 mm.

Correction for distortion in a beam outline transfer device in radiotherapy CT-based simulation.

In using a CT scanner as a radiation therapy simulator, it would be helpful to be able to transfer the beam outline from the computer plan to the patient's skin. A beam outline transfer device has been constructed and installed on a Siemens' DRH CT scanner gantry. The planned treatment beam geometry from a 3-D computerized simulation and planning system can be projected onto the patient's skin surface accurately and efficiently. The positioning accuracy achieved is within +/- 0.1 cm over a 20 cm x 20 cm field. Integrating the device into the CT scanner, simplifies the device and reduces the cost over an externally mounted device. Two unsuccessful methods to correct the projection distortions are also mentioned. In order to achieve the reported beam outline transfer accuracy, a system based on our empirically derived calibration procedure is described.

Radiotherapy departmental automation.

Cost-effective radiotherapy departmental information systems have been developed to answer a growing need for facility management and clinical research. These systems provide scheduling and management support to improve patient flow, facility utilization, charge capture, quality assurance and clinical studies. Typical data base definition, system utilization and costs are presented.

Double and multiple primary cancers in an adult head and neck radiation therapy clinic.

The records of 321 consecutive patients referred to the Radiation Oncology Center between January 1, 1980, and December 30, 1982, for head and neck cancers were reviewed to determine the incidence of other cancers. Two hundred sixty-two patients have had a single primary cancer in the head and neck region. Fifty-nine patients (18%) have had more than one cancer. These 59 patients have had 68 other cancers. While other head and neck cancers lead the list of second primaries, second cancers also occurred in the esophagus, lung, genitourinary system and elsewhere. Twenty cancers had occurred prior to the patient developing head and neck cancer. Thirty-two cancers were synchronous with the head and neck cancer; 16 have been metachronous. These numbers emphasize that patients with head and neck cancers are in a cancer-prone group that develops a variety of other cancers. These findings have important implications in work-up, radiation treatment planning, treatment goals and follow-up programs.

Initiation of C3H/10T1/2 cell transformation by N-methyl-N'-nitro-N-nitrosoguanidine and aflatoxin B1.

The utility of C3/H/10T1/2 mouse embryo fibroblasts for the detection of carcinogenic substances has been limited by their apparent insensitivity to the oncogenic effects of direct-acting alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and procarcinogens such as aflatoxin B1 (AFB1). Because the process of C3H/10T1/2 transformation can be observed to proceed through discrete stages of initiation and promotion, we have considered the possibility that MNNG and AfB1 may only initiate C3H/10T1/2 transformation. Treatment of asynchronous C3H/10T1/2 cells with MNNG or AfB1 alone generally produced few transformed foci. If MNNG or AfB1 treatment was followed by the exposure of cells to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), numerous transformed foci were produced. Phorbol did not enhance transformation by either substance. MNNG and AfB1 thus appear to be initiating agents for transformation. TPA also enhanced the transformation of C3H/10T1/2 cells by low doses of 3-methylcholanthrene (3-MCA), but transformation by high concentrations of 3-MCA was inhibited by the presence of TPA. These studied suggest that the sensitivity of the C3H/10T1/2 transformation system to potential carcinogens can be dramatically heightened if the bioassay is conducted in the presence and absence of TPA.

Initiation of C3H/10T1/2 cell transformation by formaldehyde.

The effects of formaldehyde were evaluated in the C3H/10T1/2 Cl 8 cell transformation system. Treatment of the cells with 0.1-2.5 micrograms/ml for formaldehyde alone did not result in significant rates of transformation. If formaldehyde treatment was followed by continuous treatment with 0.1 microgram/ml of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), transformed foci were produced. Methanol and formic acid lacked significant transforming activity under either treatment regimen. The results suggest that formaldehyde is an initiating agent for C3H/10T1/2 Cl 8 transformation. The fact that some compounds may act solely as initiators should be considered when this transformation system is used to study chemicals which may interact with cells by mechanisms similar to that of formaldehyde.

Data management and radiotherapy.

The realization by radiation therapists that computerized patient information is a valuable resource is slowly evolving. The uses of this data include business, quality control, and research applications. Computer applications in these areas have been limited due to the small numbers of patients and the complexity of radiation therapy problems. Reductions in costs and improved programming techniques over the last decade have made information processing computer systems feasible. Measureable progress has been made in the areas of billing and scheduling systems, improved department data handling systems, and increased participation in cooperative groups with increased data handling capability. A review of costs in terms of dollars, time, and effort supports the use of information processing systems in therapy.

Efficacy of CT-assisted two dimensional treatment planning: analysis of 45 patients.

A method is presented for quantitatively assessing the impact of CT assistance in treatment planning for radiation therapy. A three-phased analysis of treatment plans for 45 patients was undertaken. Nonuniformity and local efficiency of dose delivered were compared without and with the utilization of CT information. Good agreement between the objective assessment of treatment plans and independent subjective optimization of the plans by a radiotherapist support the validity of this technique. On the basis of nonuniformity of dose, 31 of the 45 cases were planned more poorly in the absence of CT information. The addition of CT information permitted optimization by the physician in 25 of the 45 patients. Twenty-three of these showed improved local efficiency (92%). This study indicates that measurable improvements in treatment plans are available by taking advantage of CT information. These were greatest in the brain, lung, and retroperitoneum in this small group of patients.