An automatic seed finder for brachytherapy CT postplans based on the Hough transform.

PURPOSE: The purpose of the work is to describe a new algorithm for the automatic detection of implanted radioactive seeds within the prostate. The algorithm is based on the traditional Hough transform. A method of quality assurance is described as well as a quantitative phantom study to determine the accuracy of the algorithm. METHODS AND MATERIALS: An algorithm is described which is based on the Hough transform. The Hough transform is a well known transform traditionally used to automatically segment lines and other well defined geometric objects from images. The traditional Hough transform is extended to three-dimensions and applied to CT images of seed implanted prostate glands. A method based on digitally reconstructed radiographs is described to quality assure the determined three-dimensional positions of the detected seeds. Two phantom studies utilizing eight seeds and nine seeds are described. All eight seeds form a contiguous a square while the nine seed phantom describes seeds which are placed side-by-side in groups of two and three. The algorithm is applied to the CT scans of both phantoms and the seed positions determined. RESULTS: The algorithm has been commercially developed and used to perform postsurgical dosimetric assessment on approximately 1000 patients. Using the described quality assurance tool it was determined that the algorithm accurately determined the seed positions in all 1000 patients. The algorithm was also applied to the eight seed phantom. The algorithm successfully found all eight seeds as well as their seed coordinates. The average radial error was determined to be 0.9 mm. For the nine seed phantom, the algorithm correctly identified all nine seeds, with an average radial error of 3 mm. CONCLUSIONS: The described algorithm is a robust, accurate, automatic, three-dimensional application for CT based seed determination.

Automatic detection of linear artifacts in medical images.

Our purpose in this study is to describe an algorithm for the automatic detection of linear artifacts in medical images. Linear artifacts arise as a result of many different forms of tissues and tissue boundaries within the imaging volume. Additionally, linear artifacts can arise for artificial structures such as radioactive seeds and radioactive linear sources. It is the purpose of the described algorithm to automatically detect linear artifacts of a certain length and diameter. The algorithm was written and compiled on a Pentium-4 based computer in the Microsoft Visual C/C++ language. Inert coils supplied by Radiomed Inc. were implanted into a standard prostate ultrasound phantom. Transaxial ultrasound images of the implanted phantom were obtained at 2 mm increments. The coded algorithm was then applied to the ultrasound imaging volume to automatically segment out the implanted coils. Thirteen coils were implanted in the prostate phantom. Thirteen coils were automatically identified in the imaging volume. An algorithm was developed to automatically determine the position and orientation of radioactive coils within an imaging volume. The algorithm successfully identified thirteen coils implanted in an ultrasound prostate phantom.

Preliminary treatment planning and dosimetry for a clinical trial of neutron capture therapy using a fission converter epithermal neutron beam.

A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard-MIT using a fission converter epithermal neutron beam. This epithermal neutron beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.0 g/m(2) body surface area over 90 min followed by irradiation with epithermal neutrons. Treatments were planned using NCTPlan and an accelerated version of the Monte Carlo radiation transport code MCNP 4B. Treatments were delivered in two fractions with two or three fields. Field order was reversed between fractions to equalize the average blood boron concentration between fields. The initial dose in the dose escalation study was 7.0 RBEGy, prescribed as the mean dose to the whole brain volume. This prescription dose was increased by 10% to 7.7 RBEGy in the second cohort of patients. A pharmacokinetic model was used to predict the blood boron concentration for determination of the required beam monitor units with good accuracy; differences between prescribed and delivered doses were 1.5% or less. Estimates of average tumor doses ranged from 33.7 to 83.4 RBEGy (median 57.8 RBEGy), a substantial improvement over our previous trial where the median value of the average tumor dose was 25.8 RBEGy.

Finasteride and bicalutamide as primary hormonal therapy in patients with advanced adenocarcinoma of the prostate.

BACKGROUND: Medical or surgical castration is effective in advanced prostate cancer but with profound side-effects, particularly on sexual function. Effective, less toxic therapies are needed. This study examined whether the addition of finasteride to high-dose bicalutamide enhanced disease control, as measured by additional decreases in serum prostate-specific antigen (PSA). PATIENTS AND METHODS: Forty-one patients with advanced prostate cancer received bicalutamide (150 mg/day). Finasteride (5 mg/day) was added at first PSA nadir. Serum PSA was measured every 2 weeks until disease progression. Questionnaires were administered to assess sexual function. RESULTS: Median follow-up is 3.9 years. At the first PSA nadir, median decrease in PSA from baseline was 96.5%. Thirty of 41 patients (73%) achieved a second PSA nadir and median decrease of 98.5% from baseline. Median time to each nadir was 3.7 and 5.8 weeks, respectively. Median time to treatment failure was 21.3 months. Toxicities were minor, including gynecomastia. Seventeen of 29 (59%) and 12 of 24 (50%) men had normal sex drive at baseline and at second PSA nadir, respectively. One-third of men had spontaneous erection at both time points. CONCLUSION: Finasteride provides additional intracellular androgen blockade when added to bicalutamide. Duration of control is comparable to castration, with preserved sexual function in some patients.

Feasibility and patient tolerance of a novel transrectal ultrasound hyperthermia system for treatment of prostate cancer.

This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4th edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T50) was 40.8 degrees C and mean CEM T90 = 43 degrees C was 3.4 min. Rectal wall temperature was maintained at < or = 40 degrees C. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a 'New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCI common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/- hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer.

Intraoperative treatment planning for radioactive seed implant therapy for prostate cancer.

We describe a procedure for intraoperative treatment planning for seed implantation. One hundred seven treatment plans have been analyzed at the Beth Israel Deaconess Medical Center and affiliated hospitals. The average time for the intraoperative procedure was 1. 74 hours. No significant difference in dose coverage to the prostate or normal tissues was evident.

Ultrasound image fusion for external beam radiotherapy for prostate cancer.

PURPOSE: To determine whether real-time ultrasound imaging and targeting system for the treatment of prostate cancer was feasible. The initial phase of this project included a study to develop and determine (a) software for the fusion of ultrasound images to standard x-rays obtained during simulation, and (b) the potential reduction in field size with real-time imaging. METHODS AND MATERIALS: During 13 patient simulations a transrectal ultrasound image was obtained. Orthogonal x-ray films were acquired with the rectal probe in place. Both the x-ray and ultrasound images were digitized and a fusion image was created of the prostate position in relation to the probe, bladder, and rectum. The two-dimensional area of the rectum, bladder, and prostate was determined in the lateral projection. Potential conformal blocks were designed for the lateral portals in a four-field treatment technique. RESULTS: The transrectal ultrasound probe enabled real-time prostate imaging. The lateral field size can be reduced to 6.08 x 5.68 cm2 +/- 0.62 x 0.48 cm2 from the standard 8 x 8 cm2 field. The posterior rectal wall was physically displaced out of the lateral field. The area of the rectum included in the lateral field is 1.75 cm2 +/- 0.85 cm2. CONCLUSION: The prostate position can be determined with certainty on a regular basis with transrectal ultrasonography. The amount of normal tissue in the high dose volume can be reduced. This approach may reduce acute and chronic morbidity and allow further dose escalation.

Radiotherapy for prostatic cancer: patient selection and the impact of local control.

OBJECTIVE: To analyze the long-term results of external beam radiation therapy in patients under the age of sixty treated with early-stage prostate cancer. A comparison is also made between patients with early-stage, node-negative disease and those with locally advanced node-negative prostate cancer. METHODS: In this retrospective study, 54 patients who were treated with external beam radiation, when under the age of sixty with Stanford stage T1a and T1b (equivalent to urologic stage B1), are compared to 75 patients with similar staged disease who were sixty to seventy years old at time of treatment. In addition, 17 men who underwent open lymph node dissection with Stanford stage T1a and T1b N0M0 (equivalent to urologic stage B1, pathologic node negative) were compared to 30 patients with Stanford stage T3N0M0 (equivalent to urologic stage C, pathologic node negative) prostatic carcinoma. RESULTS: Patients under the age of sixty with clinically staged early prostate cancer exhibited a similar rate of local and metastatic control when compared to men treated when sixty to seventy years of age. Overall survival was not different than the expected survival in both groups. In patients with laparotomy-proven node-negative prostate cancer, those with locally advanced tumors had a poorer rate of local control, disease-specific survival, freedom from relapse, and survival when compared to patients with early-stage disease. CONCLUSIONS: These results suggest that men under sixty years old are candidates for radiotherapy, and these results are comparable to those attained with prostatectomy. Treatment approaches for controlling bulky local disease in patients without lymph node metastases have a potential to improve local control that may have an impact on survival.

Prostate-specific antigen kinetics after external beam irradiation for carcinoma of the prostate.

PURPOSE: A mathematical model that describes the kinetics of prostate-specific antigen measured in patients who received therapeutic doses of radiation therapy is presented. The clinical implications of the model are also investigated. METHODS AND MATERIALS: Data from 122 patients treated at Stanford University between December 1985 and December 1990 were used. The general form of the model contains five parameters, two associated with a decreasing exponential, two with a rising exponential and one additional constant. A nonlinear steepest-descent procedure that minimized chi-squared was used to determine the parameters producing the best fit to a patient's data. The correlation of the model parameters with clinical findings was investigated using standard statistical techniques including multivariate life-table and logistic regression. RESULTS: The data for all patients could be fit with either a decreasing exponential with or without the additional constant (nonrelapsing pattern with two or three parameters) or with a decreasing plus rising exponential (relapsing pattern with three or four parameters). In no instance were all five parameters of the general model required to describe a patient's data. Three of 61 patients with nonrelapsing patterns experienced clinical relapse, whereas 36 of 61 patients with relapsing patterns did. The logarithm of the initial prostate-specific antigen level and the corresponding model parameter correlated with T-stage and Gleason score. Among the patients with relapsing patterns, the nadir in antigen level occurred within 2 years of the start of treatment and the time to nadir, as calculated from the model parameters, was associated with the probability of clinical relapse. In no instance was the rate of initial decline ever exceeded by the rate of subsequent rise. CONCLUSION: The model is capable of describing the kinetics of prostate-specific antigen levels found in patients after receiving radiation therapy. The parameters derived from the model are strong correlates with clinical findings and patient outcome.

Helium charged particle radiotherapy for meningioma: experience at UCLBL. University of California Lawrence Berkeley Laboratory.

PURPOSE: Evaluate the use of helium charged particle radiotherapy in the treatment of residual or unresectable meningioma adjacent to critical structures. METHODS AND MATERIALS: Twenty-nine patients with meningioma of the skull base or spine were irradiated with helium charged particle radiotherapy at the University of California Lawrence Berkeley Laboratory (UCLBL) during the period 1981-1992. Twenty-six patients were treated for intracranial and three for spinal tumors. Total doses of 53.0-80.4 Gray equivalent (GyE) with a mean of 63 GyE were delivered using the helium ion beam. RESULTS: Ten-year local control and survival rates calculated by the Kaplan-Meier product limit method were 84% and 80% respectively. Doses of 60.0 GyE were delivered with a low rate of complications. The only failures were in massive, recurrent tumors. CONCLUSION: High doses using helium charged particle radiotherapy can be safely and effectively delivered to large residual or unresectable meningioma near radiosensitive structures.

Prostate specific antigen after external beam radiotherapy for prostatic cancer: followup.

Between 1986 and 1989, 117 patients with pretreatment and serial posttreatment prostate specific antigen values received external beam radiotherapy at our hospital. Followup ranged from 0.6 to 5.9 years (mean 2.7). No patient had hormonal manipulation before distant recurrence. Biochemical relapse, defined as an increasing prostate specific antigen level after treatment, was observed in 44 patients. To date 30 of these 44 patients (68%) have had clinical relapse. The prognostic factors of advanced local stage, high Gleason score and high elevations of pretreatment prostate specific antigen values predicted for biochemical relapse and subsequent clinical failure. The interval between biochemical and clinical relapse was 156 +/- 46 days. Biochemical relapse is an important end point that can be used to determine the effect of treatment in prostatic cancer research.

Prostate cancer. Radiation therapy for localized disease.

BACKGROUND: Since 1910, a variety of radiation modalities, including radioactive isotopes, photons, and particle beams, have been used to treat prostatic cancer. METHODS: This report focuses on external beam x-irradiation produced by medium energy linear accelerators. Between 1956 and 1990, 1119 patients have been treated with curative intent at Stanford University. Tumor doses of 70 Gy delivered at 10 Gy/wk have been safe and effective. RESULTS: Fifteen-year survival rates ranging from 50%, equivalent to that of an age-matched cohort, for the least extensively localized tumors to 18% for the most extensive have been achieved. Survival is inversely proportional to clinical stage and histopathologic grade. CONCLUSION: Although external beam radiation therapy has been found to be safe and effective for the treatment of prostatic cancer, improvement in results of treatment of the more advanced tumors might be achieved by combining external beam and interstitial irradiation. This would achieve a higher radiation dose within the tumor. Alternatively, the treatment can be augmented with hyperthermia or other sensitizers in order to achieve a higher biological dose.

Radiosurgery for palliation of base of skull recurrences from head and neck cancers.

BACKGROUND: Seven patients received stereotaxic radiosurgery for 10 lesions at the base of the skull (BOS) from recurrent head and neck malignant neoplasms. METHODS: A radiation dose of 17.5-35.0 Gy was delivered as a single fraction. Follow-up ranged from 1 to 14 months. RESULTS: Nine lesions were symptomatic, and the symptoms improved in five and stabilized in four lesions. In addition, a significant radiographic response was observed in 4 of 10 recurrences. Cranial nerve signs developed in two patients, and an area of asymptomatic necrosis developed in one patient in the temporal lobe tip. CONCLUSIONS: From their brief experience, the authors conclude that stereotaxic radiosurgery may be a promising treatment in locally controlling recurrent head and neck cancers that involve the BOS.

Serum prostate-specific antigen after post-prostatectomy radiotherapy.

External beam radiotherapy was administered to 39 patients after radical prostatectomy for adenocarcinoma. Thirty-seven of 39 patients had detectable levels of serum prostate-specific antigen (PSA) prior to irradiation as evidence of residual carcinoma (biochemical evidence of disease). Two patients also had palpable recurrences. Pathologic analysis of the surgical specimens suggested that positive surgical margins, seminal vesicle or lymph node involvement, or high Gleason pattern scores are associated with measurable PSA after surgery. Follow-up ranged from two to seventy-four months (mean 26.8 months). To date, local control has been achieved in all but 1 patient (including 2 patients with palpable tumor prior to radiotherapy). Two distinct risk groups for the development of distant metastases based on the trend of the PSA in relation to the duration of follow-up after radiotherapy are defined. In the high-risk group (those patients with a rising PSA), in 9 of the 18 bone metastases have developed, while none of the 17 low-risk patients have metastatic disease.

The importance of local control in the treatment of prostatic cancer.

In a retrospective analysis of 946 patients with prostatic carcinoma treated with external beam radiotherapy between 1958 and 1989 at Stanford University Hospital the 15-year actuarial clinical local control rate was 77.8 +/- 3.3% for Stanford stage T1, 61.3 +/- 4.4% for stage T2 and 64.9 +/- 4.8% for stage T3 disease. Overall, there was improvement in disease-specific survival without a significant alteration in survival in patients who achieved clinical local control. For the 50 Stanford stage T1 cases with local control on clinical examination and a positive post-treatment biopsy a decrease in disease-specific survival was observed. There was no difference in disease-specific survival for comparable stage T2 or T3 cases. In an analysis of patients who underwent ultrasound guided prostatic biopsy performed after irradiation the trend of prostate specific antigen was more important than biopsy results in predicting which patients would have relapse.

Radiation treatment of prostate bone metastases and the biological considerations.

This contribution on the biology and management of bone metastases from prostatic cancer is divided into three parts. The first details a study conducted at Stanford University on the prevention of bone metastases in the lumbar spine, in patients in whom the lumbar spine has been irradiated coincidental to the radiation treatment of the paraaortic lymph nodes. The incidence of metastases was significantly reduced in 71 patients in whom the apparently normal lumbar spine was irradiated, as compared to the incidence of metastases in 65 patients who received no lumbar irradiation. The implications of these observations on developing strategies for early, or preemptive, irradiation for bone metastases are discussed. In the second part, the optimum radiation dose and fractionation scheme for the palliation of overt bone metastases is addressed. Drawing largely from the work of Arcangeli et al., a total dose of 40-50 Gy*, fractionated at 2 Gy per day, seems to be the regimen of choice for enduring pain relief for most patients with prostatic metastases to bone. Finally, the recent utilization of strontium-89 in the palliation of advanced bone metastases is addressed. *The Gy is the current international unit of radiation. 1Gy = 100 Rad; 1cGy (centigray) = 1 Rad.

External beam radiotherapy for incidental adenocarcinoma of the prostate discovered at transurethral resection.

This paper updates the results of 89 patients treated between 1967 and 1989 for incidental carcinoma discovered at transurethral resection of the prostate (Stanford stage T0 or AJC-UICC stage T1) with external beam irradiation. Twenty-two patients had Stanford T0 focal (less than 5% involvement of the prostatic chips) and 67 presented with Stanford T0 diffuse (5% or more involvement). Follow-up ranges from 4 months to 25.1 years, with a mean follow-up of 9.8 years. The actuarial local control for Stanford T0 focal is 100%, and 70% for Stanford T0 diffuse at 15 years. There was no difference in survival between Stanford T0 diffuse and T0 focal and the expected survival of an age-matched control population. Patients who were treated when younger than 65 had a similar local control and distant relapse when compared to those treated when 65 or older. There was no difference in local control, freedom from relapse, or disease-specific survival when the 38 patients who received irradiation to the prostate only are compared with the 29 who also received pelvic irradiation for Stanford T0 diffuse carcinoma. Patients with a Gleason score of 6 or more, when compared with those with a score of 5 or less, experienced more distant relapses and similar local control, suggesting that patients with a high grade tumor have occult metastases at presentation.

Stereotaxic radiosurgery for brain metastases: the importance of adjuvant whole brain irradiation.

Stereotaxic radiosurgery delivered from a modified 4 MV linear accelerator was used to treat 47 brain metastases in 27 patients at Stanford. Response was assessed in 41 lesions. Histopathologies included adenocarcinoma (24 lesions), renal cell carcinoma (9 lesions), melanoma (6 lesions), and squamous cell carcinoma (2 lesions). Follow-up ranged from 1.0-16.5 months, with a median of 5.0 months. Radiographic local control was achieved in 88% of the lesions. Three patients developed enlarging contrast-enhancing lesions in the radiosurgical field; one of these was biopsied and revealed necrosis with no viable tumor. Adjuvant whole brain irradiation (10 patients) was associated with regional intracranial control in 80% of patients. This was statistically superior (p = 0.0007) to the regional intracranial control rate achieved when radiosurgery alone was employed (6 patients). Most patients reported resolution of their neurologic symptoms, and were able to discontinue dexamethasone without impairment of neurologic function.