A three-field arc technique (3-FAT) for treating prostate cancer.

PURPOSE: We have previously designed two external beam radiotherapy techniques for treating prostate cancer. The seven-field, coplanar fixed beam technique resulted in dose distributions that were superior to other coplanar plans studied. The other technique using bilateral blocked arcs produced slightly higher doses to normal tissues but was far simpler to execute. We combined aspects of both these plans to produce a technique that was less complicated yet resulted in an improved dose distribution, i.e., to improve dose delivery to the clinical target volume (CTV) while minimizing doses to the rectum, bladder, and femoral heads. METHODS AND MATERIALS: Twenty patients, previously treated at the University of California, San Francisco (UCSF) with radiotherapy for adenocarcinoma of the prostate, were studied. Each patient was treated with an immobilizer, urethrogram, and a preplanning CT scan. A previously employed, seven-field, coplanar, fixed beam technique was compared with a newly designed three-field, arc technique (3-FAT). This 3-FAT was designed using two equally weighted rotational beams, with nonuniform blocks, beginning in the lateral gantry position and spanning anteriorly 35 degrees. The two beams became noncoplanar by turning the table 20 degrees, bringing the patient's feet toward the gantry (inferior oblique arcs). An anterior inferior oblique (AIO), angled 20 degrees to the inferior of anterior was included for 10% of the daily treatment. Dose-volume histograms (DVH) were used to evaluate doses to adjacent critical structures. The dose to each critical structure was averaged and tabulated for the 20 patients. In addition, we compared normalized doses to adjacent structures using 3-FAT and seven-coplanar, fixed beams vs. a technique using four noncoplanar, fixed beams. RESULTS: The three-field arc technique produced favorable dose distributions for the rectum, bladder, and femoral heads. Compared to the seven-field plan, employing the 3-FAT resulted in a 13% lower dose to 40% of the rectum, and 25% lower dose to 40% of the bladder. Compared to the four-field plan, employing the 3-FAT resulted in a 23% lower dose to 40% of the rectum, and 1% decrease in dose to 40% of the bladder. The three-field arc technique reduced the dose delivered to 40% of the femoral heads by approximately 45% when compared to the other techniques. Compared to other standard treatment techniques, the improvement in dose distribution was even greater. CONCLUSIONS: The 3-FAT represents a technical improvement in the treatment of cancer of the prostate and seminal vesicles by minimizing the dose delivered to adjacent critical structures. The 3-FAT can incorporate the advances of multileaf collimation and digitally reconstructed radiographs to deliver treatment with cost effectiveness and technological efficiency.

Pattern of recurrence of medulloblastoma after low-dose craniospinal radiotherapy.

PURPOSE: We retrospectively evaluated relapse of medulloblastoma after low- or high-dose craniospinal radiotherapy, and after conventional or hyperfractionated posterior fossa irradiation. METHODS AND MATERIALS: Ninety-two pediatric patients were treated postoperatively since 1970 at the University of California, San Francisco. Until 1989, we employed conventional fractionation with low (< or = 30 Gy) or high-dose craniospinal fields and low-dose (< or = 56 Gy) posterior fossa boosts. Recently, hyperfractionation delivered low- or high-dose to the craniospinal axis and high-dose to the posterior fossa. Most patients treated after 1979 received chemotherapy. RESULTS: Median follow-up was 70 months. Five-year disease-free survival was 36% (22% for poor-risk vs. 59% for good-risk patients). Five-year overall survival was 52% (43% for poor vs. 68% for good-risk). Neither the dose to the posterior fossa nor the craniospinal axis was statistically related to recurrence. Failure in the posterior fossa occurred despite boosts greater than 56 Gy. Females, over the age of 6 years, had significantly better relapse-free survival than males of the same age. Six of the 54 patients who relapsed were long-term survivors. CONCLUSIONS: Low-dose craniospinal radiotherapy, where the majority of patients received chemotherapy, was not associated with increased failure. High-dose posterior fossa hyperfractionation did not improve control. Long-term survival was noted in a number of patients after relapse. We recommend 60 Gy or greater with conventional fractions to the primary area, and continued study of low-dose craniospinal irradiation with adjuvant chemotherapy.

Conformal radiotherapy for brain tumors.

The technical improvements of three-dimensional conformal radiotherapy can decrease the toxicity of brain treatment to acceptable levels. The adoption of the technique by more centers would allow for the potential advantages of three-dimensional radiotherapy to be employed in a greater number of patients. Further studies evaluating the use of three-dimensional conformal radiotherapy in patients with nervous system neoplasms should focus on determining the effects on quality of life for the patient and survival compared with more standard treatment techniques.

Stereotactic radiosurgery for brain tumors.

In the 50 years since Leksell developed the concepts and initial hardware for modern brain radiosurgery, the treatment has progressed to the point where it is used commonly for arteriovenous malformations, benign masses, and metastases. Radiosurgery offers patients an effective treatment of life-threatening lesions with a reasonably low risk for discomfort and injury. In the 1990s, the procedure was used widely as primary and adjuvant treatment. The difficulty of defining the boundaries of primary brain cancers makes determining treatment targets problematic. Better imaging and computing offer a bright future for the technology.

Tamoxifen radiosensitization in human glioblastoma cell lines.

OBJECT: A combined tamoxifen and radiation therapy is being used in clinical trials to treat glioblastoma multiforme (GBM). The rationale behind this therapy is that tamoxifen is a radiosensitizer. However, the evidence for this is weak. The authors, therefore, examined the effect of combined radiation-tamoxifen therapy in three GBM cell lines of human origin. METHODS: The GBM cell lines were exposed to different concentrations (0.3-5 microg/ml) of tamoxifen and subsequently irradiated at varying doses (0.8-5 Gy). Tumor growth inhibition was measured using a proliferation assay. The interaction of tamoxifen and radiation therapies was quantified using the combination index method, which distinguishes whether a combined antitumor effect is synergistic, additive, or antagonistic. At high doses of tamoxifen or radiation there was significant inhibition of tumor cell proliferation. At low doses of either therapeutic agent, there was little effect. In one cell line, synergism occurred at high doses of tamoxifen and radiation. In the other two cell lines, an additive effect was observed. In only one of the three cell lines was there synergy between tamoxifen and radiation at doses that significantly inhibited tumor proliferation. CONCLUSIONS: Because synergy could not be demonstrated in all three cell lines at active dosages, the clinical combination of tamoxifen and radiation therapies may not be of benefit to all patients.

2-CAT: 2-concentric arc technique.

We used conventional three-dimensional (3D) planning software and blocking to design a radiation dose distribution in the shape of a hollow sphere. The technique, known as 2-CAT, employs arcing beams with blocking of the center of the field, along with partial transmission blocking of the poles of the portal. The central core can subsequently be irradiated to deliver a relatively even dose to the entire volume. The technique differs from conventional planning in that the central portion of the tumor, while surrounded, is not included in the initial treatment volume. The clinical usefulness of the method will require future testing, as the technique has not yet been clinically proven.

3D conformal radiotherapy in the sagittal plane for centrally located thoracic tumors.

One hundred patients, recently treated at the University of California, San Francisco (UCSF) with radiotherapy for lung and esophageal cancer, were studied. Three subsets of these patients were defined based on tumor location to test how commonly the use of three-dimensional (3D) conformal radiotherapy (3DCRT) could improve significantly the delivery of high dosages. Comparisons were made between isodose distributions and dose volume histograms (DVHs) of patients' prior computed tomography (CT)-based treatment plans and newly generated 3D-based treatment plans. The use of beam angles outside the conventional horizontal plane did not significantly improve the dose distribution for patients if a peripheral mass was the target volume. Patients with a target volume involving the central thorax represented a subset (> 40% of the patients) who would have benefited the most from the use of nonconventional beam angles. In these patients, sagittal coplanar beams (sagittal Y technique) reduced the dose to 30% of the lung volume from 30% to 5%. Doses to the spinal cord and heart were slightly higher than with conventional techniques but were within the tolerance of normal tissues. The sagittal Y technique allows an escalation in total dose to the tumor without increasing dose to normal tissues beyond their tolerance.

Monte Carlo model of the scanning beam digital x-ray (SBDX) source.

The scanning-beam digital x-ray (SBDX) system has been developed for fluoroscopic imaging using an inverse x-ray imaging geometry. The SBDX system consists of a large-area x-ray source with a multihole collimator and a small detector. The goal of this study was to build a Monte Carlo (MC) model of the SBDX source as a useful tool for optimization of the SBDX imaging system in terms of its hardware components and imaging parameters. The MC model of the source was built in the EGSnrc/BEAMnrc code and validated using the DOSXYZnrc code and Gafchromic film measurements for 80, 100, and 120 kV x-ray source voltages. The MC simulated depth dose curves agreed with measurements to within 5%, and beam profiles at three selected depths generally agreed within 5%. Exposure rates and half-value layers for three voltages were also calculated from the MC simulations. Patient skin-dose per unit detector-dose was quantified as a function of patient size for all three x-ray source voltages. The skin-dose to detector-dose ratio ranged from 5-10 for a 20 cm thick patient to 1 × 10(3)-1 × 10(5) for a 50 cm patient for the 120 and 80 kV beams, respectively. Simulations of imaging dose for a prostate patient using common imaging parameters revealed that skin-dose per frame was as low as 0.2 mGy.

Advances in stereotactic radiosurgery for brain neoplasms.

It has been nearly half a century since Leksell introduced brain radiosurgery. In the past decade, the procedure has become widely used as both a primary and adjuvant treatment. Radiosurgery is now commonly employed for arteriovenous malformations, brain metastases, and several benign lesions. Its use in primary brain malignancy remains of uncertain benefit. Improvements in imaging, hardware, and software promise an even greater role for the technique.

Enzymatic cleavage of a bacterial genome at a 10-base-pair recognition site.

The circular genome of Staphylococcus aureus was cut into two fragments by a simple enzymatic method that cleaves a 10-base-pair site. The recognition sequence, A-T-C-G-mA decreases T-C-G-mA-T, was created by the combined use of the methylase M.Cla I (A-T-C-G-mA-T) and the restriction endonuclease Dpn I (G-mA decreases T-C). This technique is insensitive to CpG methylation and in human DNA is predicted to produce fragments that, on average, are greater than five million base pairs. The ability to create such long pieces of DNA should facilitate mapping of large, complex chromosomes.

Influence of a child's sex on medulloblastoma outcome.

CONTEXT: Aggressive treatment of medulloblastoma, the most common pediatric brain tumor, has not improved survival. Identifying better prognostic indicators may warrant less morbid therapy. OBJECTIVE: To investigate the role of sex on outcome of medulloblastoma. DESIGN: Retrospective study of significant factors for survival with a median follow-up of 82 months. SETTING: University medical center. PATIENTS: A total of 109 consecutive, pediatric patients treated for primary medulloblastoma from 1970 to 1995 with surgery and postoperative radiotherapy and, after 1979, chemotherapy. MAIN OUTCOME MEASURES: Factors independently associated with survival. RESULTS: The final multivariate model predicting improved survival included sex (hazard ratio, 0.52; 95% confidence interval [CI], 0.29-0.92; P=.03; favoring female), metastases at presentation (hazard ratio, 2.01; 95% CI, 1.14-3.52; P=.02), and extent of surgical resection (hazard ratio, 0.60; 95% CI, 0.34-1.04; P=.07; favoring greater resection). The overall, 5-year freedom from progression was 40% and survival was 49%. Radiotherapy dose (P=.72), and chemotherapy (P=.90) did not significantly affect a disease outcome. CONCLUSIONS: The sex of the child was an important predictor for survival of medulloblastoma; girls had a much better outcome. The difference in survival between sexes should be evaluated in prospective, clinical trials.

Therapeutic Strategies for Localized Prostate Cancer II: Perineal Prostatectomy, X-Rays, Protons, Neutrons, and Combination Brachytherapy.

Application of improved imaging, diagnostic, and computer techniques is beginning to have an impact on the management of localized prostate cancer. It is possible to perform a range of surgical and radiation procedures with less morbidity than in the past. The changes in therapy for patients with localized disease derive from better knowledge of anatomy for invasive procedures and optimization of virtual planning for noninvasive methods. Perineal prostatectomy and combinations of beam and seed radiation offer both patient and physician reasonable therapeutic options.

Minimal toxicity with 3-FAT radiotherapy of prostate cancer.

Beam radiation with three-dimensional conformal planning appears to decrease morbidity of prostate cancer therapy. The 3-field, arc technique (3-FAT) technique was designed by computer modeling to improve radiation dose to the target and minimize dispersion to nearby organs. Toxicity was studied in patients with prostate cancer. We performed a retrospective study of 168 consecutive men with prostate cancer after 3-FAT radiotherapy with a median follow-up of 24 months. All patients, treated from 1996 through 1999 at the University of Colorado had a pathological diagnosis of cancer before irradiation. Therapy was designed with a urethrogram and planning computed tomography scan. The 3-FAT was employed using noncoplanar, rotational beams, and nonuniform blocking of portals. Patients were treated to a minimal tumor dose of 74 Gy in 37 fractions. Adverse effects were investigated. Definitive radiotherapy was given to 80% of the group, and 58% received total androgen blockade. 3-FAT produced favorable dose distributions for the rectum, bladder, femoral heads, and base of the penis. Patients routinely report minimal dysuria and frequency during treatment. There were minimal urinary complaints after irradiation and no proctitis, diarrhea, incontinence, or change in potency as a result of radiotherapy. The 3-FAT represents a technical improvement in the treatment of prostate cancer by minimizing radiation delivered to adjacent critical structures. There were minimal side effects to the rectum, bladder, and penis base despite high doses to the prostate and seminal vesicles. The large percentage of patients with preliminary prostate-specific antigen values below 1.0 portends efficacy.

Adult medulloblastoma: an analysis of survival and prognostic factors.

PURPOSE: This analysis aimed to review the experience in the management of adult medulloblastoma at the University of California, San Francisco, and to identify important prognostic factors for survival and posterior fossa control. PATIENTS AND METHODS: We performed a retrospective review of 34 adult patients, age > or = 15, with cerebellar medulloblastoma treated with radiotherapy at the University of California, San Francisco from 1970 to 1994. All patients underwent a surgical procedure (complete resection in 17, subtotal resection in 10, and biopsy alone in seven), followed by craniospinal irradiation. Most patients treated after 1979 also received chemotherapy. Twenty were classified as poor-risk due to either incomplete resection or evidence of disease outside of the posterior fossa at diagnosis. RESULTS: The 5-year posterior fossa control and overall survival rates were 61% and 58%, respectively. The majority of relapses occurred in the posterior fossa (14 of 17). Multivariate analysis revealed that age (favoring older patients), gender (favoring female patients), and extent of disease at diagnosis (favoring localized disease) were important prognostic factors for posterior fossa control. There was a trend toward improved posterior fossa control with higher radiation dose to the posterior fossa in patients with a complete resection. Gender and extent of disease at presentation were significant prognostic factors for survival. The 5-year survival rates were 92% for female patients versus 40% for male patients, and 67% for patients with localized disease versus 25% for those with disseminated disease. The prognosis following recurrence was poor; all died of the disease. DISCUSSION: Survival for adult medulloblastoma was comparable to its pediatric counterpart. In patients with localized disease at presentation, gender (favoring female patients) and age (favoring older patients) were important prognostic factors for posterior fossa control and survival. In patients with disseminated disease at presentation, the prognosis is poor, and innovative therapy is needed to improve survival.